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Upregulation of p53 Expression in Patients with Colorectal Cancer by Administration of Curcumin

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Abstract

Biological therapies can be beneficial in cancer patients. The present study aims to examine the inhibitory mechanism of curcumin on cancer cells in patients with colorectal cancer. The results showed that curcumin administration increased body weight, decreased serum TNF-alpha levels, increased apoptotic tumor cells, enhanced expression of p53 molecule in tumor tissue, and modulated tumor cell apoptotic pathway. We conclude that the curcumin treatment improves the general health of patients with colorectal cancer via the mechanism of increased p53 molecule expression in tumor cells and consequently speeds up tumor cell apoptosis.

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... Zhen et. al. analyzed CRC tissue for DNA fragmentation and apoptosis in light of this idea [197]. Curcumin therapy in CRC patients caused cancer cell death, similar to what was seen in animal studies [196], and this might lower the number of cancer cells in tumors. ...
... Curcumin therapy in CRC patients caused cancer cell death, similar to what was seen in animal studies [196], and this might lower the number of cancer cells in tumors. This investigation found that decreasing the number of cancer cells was associated with better weight loss and lower levels of tumor necrosis factor alpha (TNF-α) in the blood [197]. ...
... Proposed tumor suppressor p53 controls both mitochondria-dependent and mitochondria-independent apoptosis pathways and acts as an apoptosis inducer in response to numerous stresses, including DNA damage, hypoxia, and oncogenetic activation [198]. From this study it may be assumed that curcumin administration induces apoptosis in cancer cells since we detected an increase in the percentage of apoptotic cells in colorectal cancer following curcumin therapy [197]. ...
Article
Abnormalities in the mitogen-activated protein kinase (MAPK) signaling pathway are a key contributor to the carcinogenesis process and have therefore been implicated in several aspects of tumorigenesis, including cell differentiation, proliferation, invasion, angiogenesis, apoptosis, and metastasis. This pathway offers multiple molecular targets that may be modulated for anticancer activity and is of great interest for several malignancies. Polyphenols from various dietary sources have been observed to interfere with certain aspects of this pathway and consequently play a substantial role in the development and progression of cancer by suppressing cell growth, inactivating carcinogens, blocking angiogenesis, causing cell death, and changing immunity. A good number of polyphenolic compounds have shown promising outcomes in numerous pieces of research and are currently being investigated clinically to treat cancer patients. The current study concentrates on the role of the MAPK pathway in the development and metastasis of cancer, with particular emphasis on dietary polyphenolic compounds that influence the different MAPK sub-pathways to obtain an anticancer effect. This study aims to convey an overview of the various aspects of the MAPK pathway in cancer development and invasion, as well as a review of the advances achieved in the development of polyphenols to modulate the MAPK signaling pathway for better treatment of cancer.
... Of these, three were RCT and 4, quasi-experimental studies. Three articles were excluded by full-text screening, because one of the studies was conducted on pancreatic cancer patients whilst the other study was aimed at assessing the pharmacokinetic profile of curcumin, both of which are out of the scope of this systematic review (He et al., 2011;Kanai et al., 2013;Allegra et al., 2017). The third study was a protocol, which was also not within the scope of the present systematic review . ...
... As shown in Table 2, two articles were published in 2001 (Hsieh, 2001;Sharma et al., 2001) and 1 in 2004 (Carroll et al., 2011), whilst the remaining 5 between 2011 and 2019.Three articles were published in United Kingdom (Sharma et al., 2001;Carroll et al., 2011;Howells et al., 2019), two from China (Hsieh, 2001;He et al., 2011), one each from Australia and the United States. The study objectives were common to all studies, i.e., to assess the efficacy of curcumin on patients with colon cancer. ...
... The study objectives were common to all studies, i.e., to assess the efficacy of curcumin on patients with colon cancer. Only three studies were designated as a comparative study between curcumin and other interventions (He et al., 2011;Fang et al., 2014;Greil et al., 2018). The remaining studies were designated as single intervention with curcumin only (Hsieh, 2001; ...
Article
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Curcumin, obtained from curcuma longa, has been the subject of decades of scientific investigation on its therapeutic usefulness. It is reported to possess several therapeutic properties, of which anti-colon cancer is of interest in this review. Clinically however, curcumin has yet to firm up its place among established anti-colon cancer therapeutic contenders. We aimed to systematically review prevailing clinical evidence on the role of curcumin in colon cancer treatment. The review drawing from literature on clinical studies indicates fairly long term tolerability. No regression of tumor was reported when curcumin was the sole intervention. Increase in p53 level expression was reported in a placebo controlled study but no reduction in PGE2 or 5HETE. Pharmacokinetic data on healthy humans indicate that formulated curcumin delivery systems present significantly higher systemic bioavailability. It appears therefore that the clinical use of curcumin can potentially be realized only through appropriate formulation interventions. Systematic Review Registration : [website], identifier [registration number]
... After reading of articles, 14 were excluded due to differences such as administration of curcumin through oral, topical or mouthwash routes without subsequent ingestion, no access to the full study, lack of data and non-randomized studies. A schematic diagram of the search strategy is depicted in Figure 2. Of the six eligible studies, three reported the effect of curcumin on anti-inflammatory profile (He et al., 2011;Panahi et al., 2014;Thomas et al., 2014), one described reduction in dermatitis after radiotherapy (Ryan et al., 2013), three showed modification of PSA ( one study reported an effect on the profile of antioxidant enzymes (Hejazi et al., 2016). A total of 450 adults, comprising 259 individuals in intervention groups and 191 in control groups were included. ...
... The main characteristics of the studies are described in Table I. Four studies used curcumin alone (He et al., 2011;Hejazi et al., 2016;Panahi et al., 2014;Ryan et al., 2013), whereas in two studies curcumin was associated with other nutrients (Van Die et al., 2017;Thomas et al., 2014). ...
... In the study by He et al. (2011), there was a significant reduction in TNF-α percentage levels in patients treated with curcumin after 10 days of treatment (p <0.05). The results showed a negative correlation between body weight gain of patients with colorectal CA in curcumin capsule use and decreased serum levels of TNF-α (r = -0.40 ...
Article
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Feeding with high levels of phytochemicals, including curcumin, may be a therapeutic option for diseases such as cancer which is a public health problem. The aim of this study was to systematically review the results of clinical trials investigating the effect of oral curcumin supplementation on anti-inflammatory and antioxidant profiles, reduction of PSA levels and degree of dermatitis in radiotherapy treatment in cancer patients. The review was carried out based on the items of the PRISMA Statement. A bias risk assessment was performed according to Cochrane Collaboration criteria. Six studies met the eligibility criteria and were included in the systematic review. The results of this study are based on those obtained in the literature on the effect of curcumin on the anti-inflammatory profile, on reducing dermatitis, on PSA alteration and on anti-oxidant profile for a total of 450 individuals, comprising 259 in the intervention group and 191 in the control group. Some studies have reported improvement in biochemical and clinical indicators, with limited adverse effects and good tolerance. It was not possible to determine, with the desired degree of evidence, the effect of curcumin supplementation in the treatment of cancer patients. It is important to consider the great heterogeneity and methodological weaknesses of the studies, and that it was not possible to perform a meta-analysis of the data available in the literature.
... The clinical data on turmeric are scarce. In patients with colorectal cancer, turmeric reduced weight loss and decreased serum inflammatory parameters [39]. A phase II trial involving 44 patients claimed that 30-day turmeric therapy might reduce tumor size [40]. ...
... He et al. (2011) [39],Carroll et al. (2011) [40] ...
... He et al. (2011) [39],Carroll et al. (2011) [40] ...
Article
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Cancer is the second leading cause of death worldwide, after cardiovascular diseases. Increasing patients’ awareness and providing easier access to public information result in greater interest in alternative anticancer or unproven supportive therapies. Fear of cancer and limited trust in the treating physician are also important reasons leading patients to seek these methods. Trust and good communication are essential to achieving truthful collaboration between physicians and patients. Given the popularity of CAM, better knowledge about these alternative practices may help oncologists discuss this issue with their patients. This article objectively reviews the most common unconventional therapies used by cancer patients.
... Nevertheless, a marked decrease in the number of ACF was noticed in the group receiving 4 g of CUR, which was found to be linked with a marked rise in the plasma levels of CUR conjugates, which further suggeststhe action of systematically delivered CURconjugates on the decrease inACF number instead of the locally delivered CUR [182]. In a study, in individuals with colorectal cancer, He et al. [181] studied the activities of CUR on p53 expression in the colorectum tissue and the serum TNF-α levels. In total, 126 colorectal cancer patients were randomly divided into two groups receiving either the placebo or CUR (at an oral dose of 360 mg, 3 times/day) during the period ahead of surgery. ...
... A marked decrease in the serum TNF-α level was detected in the participants receiving CUR, while no such activity was found in the placebo group.A number of apoptotic cells were also elevated following CUR treatment in comparison with the baseline values, while no noticeable alteration was detected in the placebo group. In addition, CUR treatment elevated the expression of Bax and p53 and suppressed theBcl-2 expression in the colorectal tissue [181]. ...
Article
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Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase β (IκKβ), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines.
... The results suggest that the D. calcarata extracts increase cancer cell apoptosis through a p53-dependent pathway. In agreement, He et al. [125], previously concluded that the general health of patients with colorectal cancer improved following curcumin treatment through the mechanism of increased p53 molecule expression in tumour cells and as a result, speeding up tumour cell apoptosis. Curcumin-treated Caco-2 cells showed no expression of p53, while curcumin-treated HT-29 cells resulted in the significant (p ≤ 0.001) downregulation of p53 expression. ...
... Curcumin-treated Caco-2 cells showed no expression of p53, while curcumin-treated HT-29 cells resulted in the significant (p ≤ 0.001) downregulation of p53 expression. In agreement, curcumin resulted in the downregulation of p53 in HT-29 [125]. This might be due to the fact that HT-29 colorectal cancer cells are p53 mutated cells, regardless of the p53 status, curcumin is considered to be active against colorectal cancer cells [126]. ...
Article
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Colorectal cancer is the fourth leading cause of oncological-related deaths and the third most diagnosed malignancy, worldwide. The emergence of chemoresistance is a fundamental drawback of colorectal cancer therapies and there is an urgent need for novel plant-derived therapeutics. In this regard, other compounds are needed to improve the efficacy of treatment against colorectal cancer. Medicinal plants have been effectively used by traditional doctors for decades to treat various ailments with little to no side effects. Drimia calcarata (D. calcarata) is one of the plants used by Pedi people in South Africa to treat a plethora of ailments. However, the anticancer therapeutic use of D. calcarata is less understood. Thus, this study was aimed at evaluating the potential anticancer activities of D. calcarata extracts against human colorectal cancer cells. The phytochemical analysis and antioxidant activity were analysed using LC-MS, DPPH, and FRAP. The inhibitory effects and IC50 values of D. calcarata extracts were determined using the MTT assay. Induction of cellular apoptosis was assessed using fluorescence microscopy, the Muse® Cell Analyser, and gene expression analysis by Polymerase Chain Reaction (PCR). Water extract (WE) demonstrated high phenolic, tannin, and flavonoid contents than the methanol extract (ME). LC-MS data demonstrated strong differences between the ME and WE. Moreover, WE showed the best antioxidant activity than ME. The MTT data showed that both ME and WE had no significant activity against human embryonic kidney Hek 293 cell line that served as non-cancer control cells. Caco-2 cells demonstrated high sensitivity to the ME and demonstrated resistance toward the WE, while HT-29 cells exhibited sensitivity to both D. calcarata extracts. The expression of apoptosis regulatory genes assessed by PCR revealed an upregulation of p53 by ME, accompanied by downregulation of Bcl-2 and high expression of Bax after treatment with curcumin. The Bax gene was undetected in HT-29 cells. The methanol extract induced mitochondrial-mediated apoptosis in colorectal Caco-2 and HT-29 cells and WE induced the extrinsic apoptotic pathway in HT-29 cells. ME downregulated STAT1, 3, and 5B in HT-29 cells. The D. calcarata bulb extracts, therefore, contain potential anticancer agents that can be further targeted for cancer therapeutics.
... Due to CUR chemical characteristics, it is considered to be a potent anti-inflammatory phytochemical that can interact with different inflammatory pathways that generated wide range pre-clinical and clinical therapeutic potentials for CUR [9,10]. In the past decade, a growing interest was noticed in CUR-based therapies in prophylaxis and treatment for different diseases, including CVD (atherosclerosis, diabetic cardiomyopathy, arrhythmia, hypertrophic cardiomyopathy, and heart failure) [11][12][13][14][15][16][17][18][19], cancer (colon cancer, breast cancer, and multiple myeloma) [20][21][22][23][24][25][26][27], neurodegenerative diseases (Parkinson's, Alzheimer's disease, and multiple sclerosis) [8,[28][29][30], autoimmune diseases (osteoarthritis and rheumatoid arthritis) [31,32], psychological disorders [33][34][35][36][37], diabetes [38][39][40], pulmonary diseases [41][42][43], gastrointestinal disorders (gastric ulcers, indigestion, and dyspepsia) [44][45][46][47][48], ophthalmic disorders [49][50][51], and skin disorders [52][53][54]. ...
... This effect is attributable to inhibition of cardiomyocyte Due to CUR chemical characteristics, it is considered to be a potent anti-inflammatory phytochemical that can interact with different inflammatory pathways that generated wide range pre-clinical and clinical therapeutic potentials for CUR [9,10]. In the past decade, a growing interest was noticed in CUR-based therapies in prophylaxis and treatment for different diseases, including CVD (atherosclerosis, diabetic cardiomyopathy, arrhythmia, hypertrophic cardiomyopathy, and heart failure) [11][12][13][14][15][16][17][18][19], cancer (colon cancer, breast cancer, and multiple myeloma) [20][21][22][23][24][25][26][27], neurodegenerative diseases (Parkinson's, Alzheimer's disease, and multiple sclerosis) [8,[28][29][30], autoimmune diseases (osteoarthritis and rheumatoid arthritis) [31,32], psychological disorders [33][34][35][36][37], diabetes [38][39][40], pulmonary diseases [41][42][43], gastrointestinal disorders (gastric ulcers, indigestion, and dyspepsia) [44][45][46][47][48], ophthalmic disorders [49][50][51], and skin disorders [52][53][54]. ...
... Gardeazabal et al. [90] performed a prospective Mediterranean cohort study to find an association between polyphenol intake and breast cancer. They experimental on 10,713 Spanish women (middle-aged) and reported that [28,45,49,57,65,70] Suppress serum level of TNF-α and expression of p53 [92] daily consumption of polyphenols (482-893 mg/L) significantly reduced the higher risk of breast cancer in postmenopausal women. Fabian et al. [91] performed experiments on 19 women to identify the effects of flaxseed powder and muffins on breast cancer patients and revealed that daily consumption of flaxseed powder and muffins (25 g daily) for up to 5 weeks significantly inhibited the breast cancer risk by inducing apoptosis and inhibiting cell proliferation. ...
... Similarly, an 80% reduction of breast cancer risk was reported in 45 premenopausal women after daily consumption of lignan (50 mg) up to one year [91]. Another study described that a significant reduction of serum TNF-α and expression of p53 was reported in 126 colorectal cancer patients after daily intake of curcumin (360 mg thrice daily) up to 30 days [92]. The accumulative data revealed that Gierach et al. [93] experimented on 198,404 women (age between 50 and 71) to find the association between breast cancer and caffeine and reported that caffeine has no association in postmenopausal women. ...
Article
Natural products, especially polyphenols (phenolic acids, lignans, and stilbenes) are suggested to be more potent anticancer drugs because of their no or less adverse effects, excess availability, high accuracy, and secure mode of action. In the present review, potential anticancer mechanisms of action of some polyphenols including phenolic acids, lignans, and stilbenes are discussed based on clinical, epidemiological, in vivo, and in vitro studies. The emerging evidence revealed that phenolic acids, lignans, and stilbenes induced apoptosis in the treatment of breast (MCF-7), colon (Caco-2), lung (SKLU-1), prostate (DU-145 and LNCaP), hepatocellular (hepG-2), and cervical (A-431) cancer cells, cell cycle arrest (S/G2/M/G1-phases) in gastric (MKN-45 and MKN-74), colorectal (HCT-116), bladder (T-24 and 5637), oral (H-400), leukemic (HL-60 and MOLT-4) and colon (Caco-2) cancer cells, and inhibit cell proliferation against the prostate (PC-3), liver (LI-90), breast (T47D and MDA-MB-231), colon (HT-29 and Caco-2), cervical (HTB-35), and MIC-1 cancer cells through caspase-3, MAPK, AMPK, Akt, NF-κB, Wnt, CD95, and SIRT1 pathways. Based on accumulated data, we suggested that polyphenols could be considered as a viable therapeutic option in the treatment of cancer cells in the near future.
... A clinical randomized study assessed the anticancer effect of curcumin on CRC cells in 126 patients (He et al., 2011). Half of the patients received oral curcumin capsules at a dose of 360 mg/ Frontiers in Pharmacology frontiersin.org ...
Article
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Esophageal cancer (EC) is a common tumor of the gastrointestinal system and a major threat to human health. The etiology and incidence of EC vary depending on the type of pathology. Owing to the unique physiological structure of the esophagus and the poor biological behavior of EC, the treatment modalities available are limited, and the prognosis of patients is relatively poor. Curcumin is a type of natural phytochemical belonging to the class of phenolic compounds. It exerts favorable anticancer effects on various cancers. A growing body of evidence indicates that curcumin suppresses tumor development and progression by inhibiting tumor cell proliferation, invasion, and migration, thus inducing apoptosis, regulating microRNA expression, reversing multidrug resistance, and inducing sensitivity to the therapeutic effect of chemoradiotherapy. Multiple cellular molecules, growth factors, and genes encoding proteins participating in different signaling pathways interact with each other to contribute to the complex and orderly anticancer effect. The efficacy and safety of curcumin have been established in preclinical studies for EC and clinical trials for other cancers. However, the low bioavailability of curcumin limits its clinical application. Therefore, the modification of curcumin analogs, the combination of curcumin with other drugs or therapies, and the use of novel nanocarriers have been widely investigated to improve the clinical effects of curcumin in EC.
... Jeong et al. demonstrated the inhibition of NF-kB in CRC cell lines by curcumin [44]. Further, it has been suggested that the antiinflammatory properties of curcuminoids in patients with CRC can be exerted by enhancing the expression of the tumor protein p53 in tumor tissue and modulating the tumor cell apoptotic pathway [45]. In an oxaliplatin/curcumin combination study in vitro, and using an animal model, Yin et al. found that curcumin could inhibit the phosphorylation of transcription factor p65 and Bcl-2 expression and prevent oxaliplatin resistance in CRC through the suppression of TGF-β/ Smads signaling [46]. ...
Chapter
Background Colorectal cancer (CRC) is the third and the fourth most common cancer in Iranian men and women, respectively. Curcuminoids are known to exertprotective effects against several kinds of cancers. We aim to assess the effects of curcuminoids on serum pro- and anti-inflammatory cytokines and quality of life in patients with colorectal cancer undergoing chemotherapy. Material and Methods This study was a double-blind placebo-controlled trial in patients with CRC (stage 3) aged ≥20 years, who had chemotherapy after the surgery and were referred to Baqiyatallah Oncology Clinic. Patients were randomly assigned to the treatment group receiving curcuminoids capsules (500 mg/day) (n = 36), or the control group taking placebo capsules (n = 36) for 8 weeks. Erythrocyte sedimentation rate (ESR) and serum levels of C-reactive protein (CRP) and 12 pro- and anti-inflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP-1), interferon γ (IFN-γ), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF)] were measured at baseline and at the end of the intervention. The EORTC-QLQ-C30 instrument was used to assess the quality of life before and after the intervention. Statistical analyses were performed using SPSS software. Results A total of 67 subjects completed the study as three and two subjects were lost to follow-up in the curcuminoid and placebo groups, respectively. A significant change in CRP (p = 0.002) and ESR (p = 0.0001) was observed in patients supplemented with curcuminoids at the end of 8 weeks compared to placebo. Moreover, IL-1α showed a decreasing trend after curcuminoid supplementation compared to placebo (p = 0.077). A significant improvement in functional (p = 0.002) and global quality of life (p = 0.020) scales was observed in the curcuminoid group. Conclusions The results showed that curcuminoids supplementation for a period of 8 weeks (500 mg/day) can improve ESR and serum levels of CRP in stage-3 CRC subjects and improve the global quality of life and functional scales compared to placebo.
... As one of the tumor suppressor proteins, the function of p53 is a regulator of transcription. It is proposed that p53 could modulate both mitochondriadependent and mitochondria-independent apoptotic pathways (He et al., 2011). The upregulation of p53 contributed to the DNA-damage-induced cell death (Gao et al., 2011). ...
Article
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Lung cancer is the leading cause of cancer death in the world and classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). As tyrosine kinase inhibitors (TKIs), several triterpenoid saponins can target to epidermal growth factor receptor (EGFR), a widely used molecular therapeutic target, to exhibit remarkable anti-proliferative activities in cancer cells. As one of triterpenoid saponins, 20([Formula: see text])-ginsenoside Rg3 [20([Formula: see text])-Rg3] was confirmed to be an EGFR-TKI in this work. According to the quantitative real-time reverse transcription-PCR (qRT-PCR) and immunoblotting analysis, 20([Formula: see text])-Rg3 was certified to play a key role on EGFR/Ras/Raf/MEK/ERK signal pathway regulation. Our data demonstrated that 20([Formula: see text])-Rg3 might block the cell cycle at the G0/G1 phase by downregulating CDK2, Cyclin A2, and Cyclin E1. Molecular docking suggested that the combination of both hydrophobic and hydrogen-bonding interactions may help stabilizing the 20([Formula: see text])-Rg3-EGFR binding. Furthermore, their binding stability was assessed by molecular dynamics simulation. Taken together, these data provide the evidence that 20([Formula: see text])-Rg3 could prohibit A549 cell proliferation, probably by arresting the cell cycle at the G0/G1 phase via the EGFR/Ras/Raf/MEK/ERK pathway.
... In a clinical trial for colorectal cancer, oral intake of 3.6g of curcumin decreased prostaglandin E2 (a bioactive lipid that exerts many cancer and inflammatoryrelated effects) production in blood after 1 hour of administration [103]. Another study done over 126 colorectal cancer patients showed a significant increase in tumor cell apoptosis after 1,080 mg of curcumin was given daily for 10-30 days, which can be attributed to the upregulation of p53 and increase in Bax/Bcl-2 ratio in the tumor tissues [104]. Bcl-2 and Bax are the major proteins of the Bcl-2 family with roles in tumor progression [105]. ...
Article
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Cancer is one of the leading causes of death across the world. Although conventional cancer treatments such as chemotherapy and radiotherapy have effectively decreased cancer progression, they come with many dose-limiting side-effects. Phytochemicals that naturally occur in spices, fruits, vegetables, grains, legumes, and other common foods are surprisingly effective complements to conventional cancer treatments. These biologically active compounds demonstrate anticancer effects via cell signaling pathway interference in cancerous cells. In addition, phytochemicals protect non-cancerous cells from chemotherapy-induced side-effects. This paper addresses the not only the potential of phytochemicals quercetin, isoflavones, curcumin, catechins, and hesperidin in terms of cancer treatment and protection against side-effects of chemotherapy, but also methods for increasing phytochemical bioavailability.
... Curcumin is capable of targeting multiple pathways to affect cancer development and progression, becoming a potential anti-cancer agent in clinical use. Curcumin, solely or in combination with other treatments, has been validated to suppress the tumor growth or metastasis in colorectal cancer [159], prostate cancer [160], pancreatic cancer [161], breast cancer [162] and many other cancer types. Recent studies have reported that curcumin may be a potential agent for improving the response of immune therapy. ...
Article
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The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.
... This treatment significantly reduced the number and size of ileal and rectal adenomas, compared with the baseline (60.4% and 50.9%, respectively), without toxicity. Other studies demonstrated that a daily dose of curcumin (3.6 g in capsule form) improves the general health of colorectal cancer patients by increasing p53 molecule expression in tumor cells, and consequently, inducing tumor cell apoptosis [86,120]. ...
Article
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Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.
... 228 It has shown benefits in diseases such as inflammatory conditions, kidney conditions, metabolic syndrome and pain, most of which have been attributed to its anti-inflammatory and antioxidant activities. 228 Importantly, it has also demonstrated anti-cancer potentials both preclinically and clinically in oral, 229 breast, 230-233 colorectal, 234 pancreatic, 235 skin 236 as well as head and neck 237 cancers. Specifically, the anti-BC activities of curcumin have been linked to the modulation of cell cycle regulators and metastasis-related markers; the induction of caspase-dependent apoptosis and mitochondrial apoptotic pathway; the suppression of PI3K/ AKT/mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK), NF-κB and β-catenin signalling pathways; the activation of p53 signalling pathway; as well as the inhibition of angiogenesis. ...
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Despite recent advances in the diagnosis and treatment of breast cancer (BC), it remains a global health issue affecting millions of women annually. Poor prognosis in BC patients is often linked to drug resistance as well as the lack of effective therapeutic options for metastatic and triple-negative BC. In response to these unmet needs, extensive research efforts have been devoted to exploring the anti-BC potentials of natural products owing to their multi-target mechanisms of action and good safety profiles. Various medicinal plant extracts/essential oils and natural bioactive compounds have demonstrated anti-cancer activities in preclinical BC models. Despite the promising preclinical results, however, the clinical translation of natural products has often been hindered by their poor stability, aqueous solubility and bioavailability. There have been attempts to overcome these limitations, particularly via the use of nano-based drug delivery systems (NDDSs). This review highlights the tumour targeting mechanisms of NDDSs, the advantages and disadvantages of the major classes of NDDSs and their current clinical status in BC treatment. Besides, it also discusses the proposed anti-BC mechanisms and nanoformulations of nine medicinal plants' extracts/essential oils and nine natural bioactive compounds; selected via the screening of various scientific databases, including PubMed, Scopus and Google Scholar, based on the following keywords: "Natural Product AND Nanoparticle AND Breast Cancer". Overall, these nanoformulations exhibit improved anti-cancer efficacy against preclinical BC models, with some demonstrating biocompatibility with normal cell lines and mouse models. Further clinical studies are, however, warranted to ascertain their efficacy and biocompatibility in humans.
... Further, curcumin enhances the expression of p53, a cell cycle mediator, implicated in the pathophysiology of many malignant tumors including cervical cancer, high-grade ovarian carcinoma, endometrial cancer, and even colorectal cancer particularly in a time and dose-dependent manner [20,21]. ...
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Curcumin is a commonly used herbal supplement purported for its antioxidant, anti-inflammatory, and antineoplastic properties. The effects of curcumin supplementation on endometrial lining have been proposed; however, endometrial preparation in the case of frozen-thawed embryo transfer (FET) has not been established. This case series references two scenarios where turmeric was ingested by the patient, and endometrial thickness was subsequently reduced disrupting the FET cycle. Throughout this case series, curcumin's possible interactions with the uterine lining are summarized. Additionally, these cases highlight the importance of physicians' awareness of taking a full history of any herbal remedies or supplements in addition to prescription or over-the-counter medications taken when undergoing treatment for controlled FET cycles or in-vitro fertilization (IVF). To our knowledge, no studies to date have investigated this relationship.
... In a combination study, curcumin, and quercetin (1440 + 60 mg/day for six months) were shown to reduce the number and size of polyps in patients with familial adenomatous polyposis, a hereditary disorder characterized by the development of hundreds of colorectal adenomas which turn malign when left untreated [64]. In chemotherapy, 1 g/day curcumin for up to one month (prior to surgical removal of the tumor) was shown to improve the patient's body weight and to increase the apoptosis rates of the patient's tumor cells [65]. ...
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This review deals with the various aspects involved in the medicinal action of curcumin, from the photosensitivity and its relevance to storage and shelf-life, to the different routes of administration, which influence the bioavailability. The focus of the review is on the antitumor properties of curcumin and the currently available solutions for their amelioration. The work starts by presenting a brief historical perspective on the origins and uses of curcumin, from early days until the present time. The following sections describe the physico-chemical properties of curcumin and their impact on the biological activity and pharmacokinetics, raising awareness to the need for formulations able to improve the bioavailability. The last section is focused on research efforts being made to circumvent curcumin’s instability and low availability due to the extensive hepatic first pass metabolism, describing innovative scientific advances and new patented formulations and emerging products on the market.
... Another study conducted in our laboratory revealed its chemopreventive efficacy against the lung carcinogenesis induced by B (a)P, a potential environmental carcinogen found in cigarette smoke and deep-fried food, in Swiss albino mice (Puliyappadamba et al., 2015). Curcumin treatment has a significant impact on improving the general health of colorectal cancer patients by enhancing expression of p53 molecules in tumour cells and also by promoting the apoptosis of tumour cells (He et al., 2011;Pricci et al., 2020). Curcumin intake causes the down-regulation of NF-kB, COX-2 and phosphorylated STAT3 in peripheral blood mononuclear cells from patients with pancreatic cancer (Dhillon et al., 2008). ...
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Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associated with conventional chemotherapies decrease the success rates of the existent chemotherapeutic regimen, which warrants the need for an efficient and safer alternative therapeutic approach. In this scenario, chemopreventive agents have been proven to be successful in protecting the high-risk populations from cancer, which further validates chemoprevention strategy as rational and promising. Clinical studies have shown the effectiveness of this approach in managing cancers of different origins. Phytochemicals, which constitute an appreciable proportion of currently used chemotherapeutic drugs, have been tested for their chemopreventive efficacy. This review primarily aims to highlight the efficacy of phytochemicals, currently being investigated globally as chemopreventives. The clinical relevance of chemoprevention, with special emphasis on the phytochemicals, curcumin, resveratrol, tryptanthrin, kaempferol, gingerol, emodin, quercetin genistein and epigallocatechingallate, which are potential candidates due to their ability to regulate multiple survival pathways without inducing toxicity, forms the crux of this review. The majority of these phytochemicals are polyphenols and flavanoids. We have analyzed how the key molecular targets of these chemopreventives potentially counteract the key drivers of chemoresistance, causing minimum toxicity to the body. An overview of the underlying mechanism of action of these phytochemicals in regulating the key players of cancer progression and tumor suppression is discussed in this review. A summary of the clinical trials on the important phytochemicals that emerge as chemopreventives is also incorporated. We elaborate on the pre-clinical and clinical observations, pharmacokinetics, mechanism of action, and molecular targets of some of these natural products. To summarize, the scope of this review comprises of the current status, limitations, and future directions of cancer chemoprevention, emphasizing the potency of phytochemicals as effective chemopreventives.
... However, on account of its quick metabolism and low concentration within tumors, no substantial anticancer effect is observed in vivo following exposure of mice to either 20 or 30 mg/kg 10058-F4 [12]. Curcumin has been used to treat numerous types of cancer, including colorectal cancer, either alone or in conjunction with other treatments [28,29], breast cancer [30,31], lung cancer [32], prostate cancer [33], and liver cancer [34]. e potent antineoplastic properties of curcumin against different cancers are due to proapoptotic, antiproliferative, proapoptotic, and anti-inflammatory mechanisms [15,16,35]. ...
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Background: Pancreatic cancer (PC) stands out as one of the most lethal cancers. Due to late diagnosis, only a fraction of patients can be resected. Although it still has significant adverse effects and poor results, the treatment is connected with better overall survival than the prior treatment. Thus, new alternative therapy for advanced PC is needed. Materials/Methods. The impact of 10058-F4 and curcumin combination therapy on apoptosis and cell growth in SW1990 pancreatic cancer cells were determined in vitro using the CCK-8 assay and flow cytometry of Annexin V-FITC/PI, and the in vivo antitumor effect was determined utilizing SW1990-bearing pancreatic tumor mouse models induced by subcutaneous implantation. Results: At concentrations of (10 mol/L+2 mol/L), 10058-F4+curcumin obtained the highest rate of SW1990 cell death, and they had a beneficial effect on SW1990 pancreatic tumor-bearing animals. Furthermore, c-Myc, Akt phosphorylation, and the expression of apoptosis-related molecular were reduced, and the combination therapy modified the expression of apoptosis-related molecular. Conclusions: In vitro and in vivo, the combination of 10058-F4 plus curcumin has antipancreatic cancer actions that are substantially effective.
... The authors indicated that curcumin therapy, through the mechanism of increased p53 expression in tumor cells and tissues, can improve the ordinary fitness of CRC patients. However, to validate these arguments, further studies are required [76]. ...
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Curcumin, an important constituent of turmeric used in the traditional medicinal system has suffered considerable controversy. Classification as pan-assay interference compounds and invalid metabolic panaceas contributed toward its inability as a lead compound. The conclusions were drawn on the basis of various clinical trials that failed to prove the medicinal effect of curcumin. The inclusion of high throughput screening studies also contributed to this entitlement. Still, researchers didn't put an end to explore on cur-cumin probably due to the traditionally accepted role of turmeric in medicines. Extensive investigation on curcumin multiplied enormously and more than 27,000 documents results in Scopus with one click on cur-cumin. It being a pharmacologically significant molecule or "Much Ado about Nothing" will always be debatable. In the present review, we have compiled successful clinical trials with curcumin in several diseased conditions including the results of such clinical trials where the prescribed medicine failed to respond.
... This ties in with the fact that advanced-age primary tumors are characterized by increased EGFR expression and these patients may have developed primary tumors at late stages of their life, leading to worse prognosis. 8 Clinical Medicine Insights: Oncology Regarding IDH1, a 2012 study by Sipayya et al 27 found that GBM patients had 9.7% (7/72) IDH1-positive specimens in a total of 195 gliomas. However, another study correlating the expression of IDH1 mutant protein using IHC detected no positive samples in GBM patients of India. ...
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Introduction Glioblastoma multiforme (GBM) is one of the deadliest cranial tumors occurring in adults. Various biomarkers have been tested for their significance in diagnosis, prognosis, and treatment of GBM. Some well-studied markers in GBM are Isocitrate dehydrogenase 1 (IDH1), Murine double minute 2 (MDM2), Epidermal Growth Factor Receptor (EGFR), and p53. The aim of this study was to investigate the protein expression of these markers in GBM patients of Pakistan. Methods A total of 102 surgically resected formalin-fixed paraffin-embedded specimens from patients diagnosed and treated at Aga Khan University Hospital were included in this study. Immunohistochemistry (IHC) for IDH1, MDM2, EGFR, and p53 was performed using Dako EnVision System and respective monoclonal antibodies. Survival analysis was performed to check association of markers protein expression with prognosis in GBM patients. Results There were 73 males and 29 females in this study, with a median age of 49 years at the time diagnosis. Overexpression of molecular markers was as follows: 52% for EGFR, 26% for p53, 72% for IDH1, and 83% for MDM2. We did observe that EGFR was significantly associated with increased age of our patients and with worse survival. Age > 40 years was a predictor for worse prognosis as well. Conclusion EGFR overexpression and advanced age were worse prognostic indicators.
... The anti-cancer effects of CUR on CRC cells are widely known, which is associated with activation of the apoptotic pathway [20]. Extensive studies on the underlying mechanism of apoptosis by CUR in CRC have reported several molecular targets, including enzymes such as COX-2 [37], SOD and ROS [38], transcription factors (such as catenin, NF-κB, AP-1 and PPAR-γ) [39,40], members of the Bcl-2 family, BH3 protein (such as Bim, Bad and Bid) [41], protease enzymes (such as caspase 3 and caspase 8), death receptors (such as DR5 and Fas) and other important signaling pathways such as p53, phosphoinositide-3 kinase/protein kinase-B (PI3K/Akt), JNK and ER stress [42]. It should be noted that cancer progression is a multiphase, multi-gene and multi-factor process. ...
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... In a clinical study on patients with CRC, CUR resulted in favorable effects, such as decreased serum tumor necrosis factor (TNF)-α levels, increased apoptotic tumor cells, enhanced expression of the p53 molecule in tumor tissue, and modulation of the tumor cell apoptosis pathway, suggesting that CUR can improve the general health of these patients by increasing p53 expression in tumor cells and enhancing tumor cell apoptosis (He et al. 2011). ...
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... It has been reported that curcumin can induce apoptosis in human colon cancer HT29 cells [64]. In chemo-resistant CRC cells, curcumin can enhance the therapeutic potential of conventional chemotherapeutic drugs by inhibiting proliferative targets, including cyclin D1, NF-κB, phosphoinositide 3-kinase and Src [65]. Resveratrol, a natural stilbene found in wine and grapes, has been reported to inhibit signaling pathways involved in [66]. ...
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Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.
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Phenolic compounds are secondary metabolites found in most plant tissues, including fruits and vegetables. They are produced via shikimic acid and phenylpropanoid pathways. The most common classification implies the subdivision of phenolic in two main groups: flavonoids (e.g., anthocyanins, flavanols, flavanones, flavonols, flavonones, and isoflanones) and non-flavonoids (e.g., phenolic acids, coumarins, stilbenes, lignans, lignins and tannins) polyphenols. Such variations give them a wide range of biological and potential therapeutic activities such as antioxidant, anti-inflammatory and anticancer, among others. Their structures and functions are much discussed by previous researchers. This review provides a comprehensive overview of phenolic compound structures and properties.
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ead the full text About Share on Abstract Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers.
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Zerdeçalın başlıca kimyasal bileşenlerinden biri olan kurkumin [1,7-bis (4-hidroksi-3-metoksifenil) -1,6-heptadien-3,5-dion], Curcuma Longa bitkisinin rizomundan kaynatma, kurutma gibi işlemler ile üretilir. Kurkumin farmakolojik olarak, Çin ve Hindistan tıbbında yaklaşık 6000 yıldır geleneksel bir tıbbi ajan olarak kullanılmaktadır. Gıda ve İlaç İdaresi (FDA) kurkumini “genellikle güvenli olarak tanınan” bir bileşik olarak onaylanmıştır. Çalışmalar ile kurkuminin bağırsak mikrobiyotası üzerine etki ederek yarar sağlayabileceği öngörülmektedir. Bazı çalışmalar kurkuminin, inflamasyonu baskılaması başta olmak üzere, çeşitli mekanizmalar aracılığıyla, inflamatuvar bağırsak hastalıkları, kolorektal kanser ve hepatik fibroz dahil olmak üzere H.pylori, pankreatit ve gut permeabilitesini sağlamada yararlı etkilere sahip olduğunu göstermiştir. Besin-ilaç etkileşimleri ve gebe, laktasyon ve çocuklarda kurkumin kullanımındaki belirsizlikler ve çalışma sonuçlarındaki farklılıklar da göz önüne alındığında, gastointestinal hastalıklarda kurkuminin etkisini açıklamak için daha fazla çalışmaya ihtiyaç duyulmaktadır.
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Turmeric (Curcuma longa L.) is widely utilized as a spice, food colorant, and preservative in India, China, and SouthEast Asia. With containing potential turmeric extracts and compounds, it has been utilized in traditional medicine for various diseases counting diabetes, hepatitis, hemorrhoids, hysteria, indigestion, skin disease, inflammation, anorexia, hepatic disorders, cough, and sinusitis, etc. So far, a large number of work has been conducted to find and prove biological activities and pharmacological applications of turmeric and its extracts in both animals and humans. In particular, curcumin (diferuloylmethane), a characteristic component with major yellow bioactive turmeric feature, has been found to possess numerous biological actions. Nonetheless, the polyphenol compound in curcumin has been limited for human disease treatments even though adequate studies are utilized in animal trials. Plenty of ongoing studies are also contributing significantly to this promising molecule that to the forefront of human therapeutics as well as its activities in health benefits. Thus, curcumin and some turmeric extracts are considered as non-toxic and highly promising compounds with a lot of potentially biological functions based on an appropriately used dose. It is expected that curcumin and some turmeric extracts can be explored in novel medical applications in the future to effectively against or treat various diseases. Here, we hope that it is likely a good and right approach for using and encouraging this product, and its chemical components and effective clinical applications will be briefly summarized in disease treatments. Cite this: Vo TS, Vo TTBC, Vo TTTN, Lai TNH. Turmeric (Curcuma longa L.): Chemical components and Their Effective Clinical Applications. JOTCSA. 2021;8(3):883-98.
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ÖZ: Bitkisel ürünler insanlık tarihi boyunca çeşitli amaçlarla kullanılmıştır. Bu ürünlerin çoğu, ilaçların keşfi ve tasarımında yararlanılabilecek farmakolojik veya biyolojik aktiviteye sahiptir. Zerdeçal, zencefil ailesinin bir üyesi Kurkuma longa bitkisinden elde edilmiştir. Zerdeçal, Hint ayurvedik tıbbında ve Unani geleneksel tıbbında en az 2500 yıldır sindirim ve karaciğer hastalıkları, deri enfeksiyonları ve artrit tedavisinde kullanılmaktadır. İlk kez 1815'te Vogel ve Pelletier tarafından zerdeçaldan izole edilmiş olan kürküminin 1870'de saf ve kristal formu, 1910'da ise diferuloilmetan yapısı bulunmuştur. Zerdeçalın 100 gramında; 390 kcal, toplam 10 g yağ, 3 g doymuş yağ, 0 mg kolesterol, 0.2 g kalsiyum, 0.26 g fosfor, 10 mg sodyum, 2500 mg potasyum, 47.5 mg demir, 0.9 mg tiamin, 0.19 mg riboflavin, 4.8 mg niasin, 50 mg askorbik asit, toplam 69.9 g karbonhidrat, 21 g diyet lifi, 3 g şeker ve 8 g protein bulunmaktadır. Zerdeçaldaki ana biyoaktif bileşen olan kürkümin, antioksidan, anti-inflamatuar, anti-bakteriyel ve anti-aterosklerotik özelliklere sahiptir. Bu özellikleri zerdeçalı, Alzheimer, kanser, kardiyovasküler hastalıklar, diyabet, obezite ve depresyon gibi pek çok hastalığın tedavisinde ilgi çekici kılmıştır. Bu derlemede zerdeçalın genel sağlık üzerine etkilerinin irdelenmesi amaçlanmıştır. ABSTRACT Herbal products have been used for various purposes throughout human history. Many of these products have pharmacological or biological activity that can be utilized in the discovery and design of drugs. Turmeric is derived from the Curcuma longa plant, a member of the ginger family. Turmeric has been used in Indian Ayurvedic medicine and Unani traditional medicine for at least 2500 years to treat digestive and liver diseases, skin infections and arthritis. Curcumin, which was first isolated from turmeric by Vogel and Pelletier in 1815, was found in its pure and crystalline form in 1870 and its diferuloylmethane structure in 1910. In 100 grams of turmeric; 390 kcal, 10 g total fat, 3 g saturated fat, 0 mg cholesterol, 0.2 g calcium, 0.26 g phosphorus, 10 mg sodium, 2500 mg potassium, 47.5 mg iron, 0.9 mg thiamine, 0.19 mg riboflavin, 4.8 mg niacin, 50 mg ascorbic acid, a total of 69.9 g carbohydrates, 21 g dietary fiber, 3 g sugar and 8 g protein. Curcumin, the main bioactive ingredient in turmeric, has antioxidant, anti-inflammatory, anti-bacterial and anti-atherosclerotic properties. These properties have made turmeric interesting in the treatment of many diseases such as Alzheimer's, cancer, cardiovascular diseases, diabetes, obesity and depression. In this review, it is aimed to examine the effects of turmeric on general health.
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Curcumin [1,7‐bis(4‐hydroxy‐3‐methoxyphenyl) ‐1,6‐heptadiene‐3,5‐dione] is pharmacologically active polyphenol isolated from rhizome Curcumin longa L and is a versatile molecule known for its various biological properties including anti-inflammatory, antioxidant, antibacterial, including antibacterial, anticancer, arthritis, allergies and other various chronic diseases. In recent years this compound has attracted considerable attention due to multimodal effects. In this endeavor, novel curcumin derivatives have also been synthesized and tested against different models of human disease. The current chapter is a compilation of existing information from many recent studies utilizing curcumin in various disease conditions and the new drug delivery approach to tackle bioavailability issues have also been discussed. Further the ongoing clinical studies on curcumin in various disease conditions are also reviewed in this chapter.
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Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapyrepresent effective strategies for treatment. However, in some cases with high metastatic activityand high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods isinsufficient and results in treatment failure and reduced patient survival. CTCs are seen not onlyas an isolated phenomenon but also a key inherent part of the formation of metastasis and a keyfactor in cancer death. This review discusses the impact of NSCLC therapy strategies based on ameta-analysis of clinical studies. In addition, possible therapeutic strategies for repression whenstandard methods fail, such as the administration of low-toxicity natural anticancer agents targetingthese phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in thecontext of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis(mechanisms related to tumour-associated and -infiltrating cells, epithelial–mesenchymal transition,and migration of cancer cells).
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Cancer is a significant public health issue, as well as constituting one of the main causes of death with a drastic increase. Curcumin, an active ingredient of turmeric with yellow pigment properties, is a phytochemical that has been utilized in herbal medicine to treat a variety of diseases. Due to its antioxidant, anti-inflammatory, anti-fungal, anti-bacterial, anti-viral, and anti-angiogenic effects, it has been used in a wide range of therapeutic areas. Research findings on cancer of curcumin from cell models and human clinical trials have been reviewed. Potential mechanisms of curcumin, curcumin analogs, curcumin metabolites, on various cancers, are revised through their chemical, physical properties, bioavailability, physiological activities in this direction. Even at high doses, curcumin is known as well-tolerated and non-toxic. Laboratory studies have hitherto disclosed positive results, vis-à-vis the anti-cancer and chemo preventive properties viz. antioxidant, anti-inflammatory, anti-proliferative, anti-metastatic, anti-invasion activities, apoptosis, autophagy inducer curcumin holds. Curcumin has been corroborated to prevent carcinogenesis by modulating the cell cycle by binding molecular targets such as transcription factors, growth factors, inflammatory cytokines, specific genes, certain enzymes like kinases. Thence, arguably curcumin can make a difference in cancer treatment in the future, considering its advantages anent possible mechanisms, toxicity, and cost.
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Nanoparticles have emerged as promising drug delivery systems for the treatment of several diseases. Novel cancer therapies have exploited these particles as alternative adjuvant therapies to overcome the traditional limitations of radio and chemotherapy. Curcumin is a natural bioactive compound found in turmeric, that has been reported to show anticancer activity against several types of tumors. Despite some biological limitations regarding its absorption in the human body, curcumin encapsulation in poly(lactic-co-glycolic acid) (PLGA), a non-toxic, biodegradable and biocompatible polymer, represents an effective strategy to deliver a drug to a tumor site. Furthermore, PLGA nanoparticles can be engineered with targeting moieties to reach specific cancer cells, thus enhancing the antitumor effects of curcumin. We herein aim to bring an up-to-date summary of the recently developed strategies for curcumin delivery to different types of cancer cells through encapsulation in PLGA nanoparticles, correlating their effects with those of curcumin on the biological capabilities acquired by cancer cells (cancer hallmarks). We discuss the targeting strategies proposed for advanced curcumin delivery and the respective improvements achieved for each cancer cell analyzed, in addition to exploring the encapsulation techniques employed. The conjugation of correct encapsulation techniques with tumor-oriented targeting design can result in curcumin-loaded PLGA nanoparticles that can successfully integrate the elaborate network of development of alternative cancer treatments along with traditional ones. Finally, the current challenges and future demands to launch these nanoparticles in oncology are comprehensively examined.
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Curcuma longa and its constituents, mainly curcumin, showed various of pharmacological effects in previous studies. This review article provides updated and comprehensive experimental and clinical evidence regarding the effects of C. longa and curcumin on respiratory, allergic, and immunologic disorders. Using appropriate keywords, databases including PubMed, Science Direct, and Scopus were searched until the end of October 2021. C. longa extracts and its constituent, curcumin, showed the relaxant effect on tracheal smooth muscle, which indicates their bronchodilatory effect in obstructive pulmonary diseases. The preventive effects of extracts of C. longa and curcumin were shown in experimental animal models of different respiratory diseases through antioxidant, immunomodulatory, and anti-inflammatory mechanisms. C. longa and curcumin also showed preventive effects on some lung disorders in the clinical studies. It was shown that the effects of C. longa on pulmonary diseases were mainly due to its constituent, curcumin. Pharmacological effects of C. longa extracts and curcumin on respiratory, allergic, and immunologic disorders indicate the possible therapeutic effect of the plant and curcumin on these diseases.
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Cancer cachexia-associated weight loss is poorly understood; energetically demanding tissues (eg, organ and tumor mass) and resting energy expenditure (REE) are reported to increase with advanced cancer. The objective was to quantify the potential contribution of increasing masses of energetically demanding tissues to REE with colorectal cancer cachexia progression. A longitudinal computed tomography (CT) image review was performed to quantify organ size (liver, including metastases, and spleen) and peripheral tissues (skeletal muscle and adipose tissue) during colorectal cancer cachexia progression (n = 34). Body composition was prospectively evaluated by CT and dual-energy X-ray absorptiometry, and REE was determined by indirect calorimetry in advanced colorectal cancer patients (n = 18). Eleven months from death, the liver (2.3 +/- 0.7 kg) and spleen (0.32 +/- 0.2 kg) were larger than reference values. One month from death, liver weight increased to 3.0 +/- 1.5 kg (P = 0.010), spleen showed a trend to increase (P = 0.077), and concurrent losses of muscle (4.2 kg) and fat (3.5 kg) (P < 0.05) were observed. The estimated percentage of fat-free mass (FFM) occupied by the liver increased from 4.5% to 7.0% (P < 0.001). The most rapid loss of peripheral tissues and liver and metastases gain occurred within 3 mo of death. A positive linear relation existed between liver mass and measured whole-body REE (r(2) = 0.35, P = 0.010); because liver accounted for a larger percentage of FFM, measured REE . kg FFM(-1) . d(-1) increased (r(2) = 0.35, P = 0.010). Increases in mass and in the proportion of high metabolic rate tissues, including liver and tumor, represented a cumulative incremental REE of approximately 17,700 kcal during the last 3 mo of life and may contribute substantially to cachexia-associated weight loss.
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The infection with Friend murine leukemia virus (FMuLv) is being used as a retrovirus infection model for searching the potential anti-viral medicinal preparations or establishing new treatment strategies. In the present study we have evaluated the inhibitory effect of three non-toxic antiviral natural compounds namely berberine, curcumin or picroliv against FMuLv induced erythroleukemia in BALB/c mice. To understand the effect of these compounds in the initiation and progression of leukemia we did a series of analysis, which include hematological and biochemical parameters, histopathological evaluations of the liver and the spleen and expression analysis of selected genes such as Bcl-2, p53, p45NFE2, Raf-1, Erk-1, IFNgamma receptor and erythropoietin in spleen. The treatment with berberine, curcumin or picroliv were found to (a) elevate the life span of leukemia harboring animals by more than 60 days; (b) decreased the anemic condition which was highly prevalent in FMuLv alone treated group; (c) histopathological evaluations showed that the compounds tested here inhibited the massive leukemic cell infiltrations to sinusoidal spaces in spleen; (d) decrease the expression of Bcl-2, Raf-1, Erk-1 IFNgamma receptor and erythropoietin; (e) induce the expression of p53. Overall, our results suggest that berberine, curcumin and picroliv were able to suppress the progression of leukemia induced by FMuLv and further support their chemopreventive potential against virally induced cancers.
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Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a combination of naturally oncolytic viruses and wild-type viruses rendered oncolytic and harmless by genetic engineering, that will induce complete remissions of human tumors. It may be necessary to co-administer certain chemotherapeutic agents, advanced cancer vaccines, or even immune lymphocytes, and targeted therapeuticals, to ascertain, that remissions induced by the viral agents will remain complete and durable; will co-operate with anti-tumor host immune reactions, and eventually will result in cures of advanced metastatic human cancers.
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Curcumin, a natural compound derived from tumeric, has been shown to induce apoptosis in the leukemic cell line K562 and other cancer cell lines. However, it is unknown whether curcumin also has an inhibitory effect on BCR-ABL-expressing B-lymphoid cells. We tested whether curcumin has an inhibitory effect on BCR-ABL B-cell acute lymphoblastic leukemia (B-ALL) in vitro and in vivo. Pre-B cells isolated from B6 mice expressing wild-type BCR-ABL (B6p210) and T315I mutant (B6T315I) were cultured in serial concentration of curcumin. Cultured cells were analyzed by automated cell counter, flow cytometry, western blotting, and transcription factor arrays. B-ALL was induced by transplantation of MSCV-GFP-p210 transduced donor marrow in lethally irradiated Balb/c mice. Diseased mice were treated with placebo or curcumin until death of the mice. Diseased mice were analyzed by flow cytometric and histopathological analyses. Curcumin inhibited the proliferation of B6p210 and B6T315I cells at concentration as low as 10 muM and induced apoptosis of the cells at concentrations of 30 muM. Using western blots and transcription factors arrays, we showed that curcumin decreased NF-kappaB levels and increased p53 levels. Curcumin decreased c-Abl levels in cells expressing the wild, but not the mutant, BCR-ABL oncogene. Curcumin treatment resulted in a statistically significant improved survival in diseased mice along with decreasing white blood and GFP cell counts. Curcumin is effective against leukemic cells expressing p210 BCR-ABL and T315I BCR-ABL and holds promise in treating BCR-ABL-induced B-ALL.
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The present study aims to access the effects of sophora alkaloids on the production of pro-inflammatory cytokines and evaluate their therapeutic efficiency on cachexia. The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages, and sophocarpine showed the most potent inhibitory effect among them. Quantification of TNF-alpha and IL-6 mRNA in RAW264.7 cells by real-time RT-PCR revealed that both sophocarpine and matrine suppressed TNF-alpha and IL-6 expression and sophocarpine has stronger suppressing potency than matrine. Inoculation (s.c.) of colon26 adenocarcinoma cells into BALB/c mice induced cachexia, as evidenced by progressive weight loss, reduction in food intake, wasting of gastrocnemius muscle and epididymal fat, and increase in serum levels of TNF-alpha and IL-6. Administration of 50 mg/kg/d sophocarpine or matrine for 5 days from the onset of cachexia did not inhibit the tumor growth but resulted in attenuation of cachexia symptoms. Furthermore, sophocarpine and matrine decreased the serum levels of TNF-alpha and IL-6, and sophocarpine showed a better therapeutic effect than matrine. These results suggest that sophocarpine and matrine exert anti-cachectic effects probably through inhibition of TNF-alpha and IL-6.
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The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.
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During the past 20 years, the flowering plant Arabidopsis thaliana has been adopted as a model organism by thousands of biologists. This community has developed important tools, resources and experimental approaches that have greatly stimulated plant biological research. Here, we review some of the key events that led to the uptake of Arabidopsis as a model plant and to the growth of the Arabidopsis community.
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Cachexia — the massive (up to 80%) loss of both adipose tissue and skeletal muscle mass — is a significant factor in the poor performance status and high mortality rate of cancer patients. Although this metabolic defect has been known since cancer was first studied, it is only recently that major advances have been made in the identification of catabolic factors that act to destroy host tissues during the cachectic process. Although anorexia is frequently present, depression of food intake alone seems not to be responsible for the wasting of body tissues, as nutritional supplementation or pharmacological manipulation of appetite is unable to reverse the catabolic process — particularly with respect to skeletal muscle. However, recent clinical studies in cancer patients have shown that nutritional supplementation can be effective when combined with agents that attenuate the action of tumour factors and modifiers of the central effects on appetite might also show promise.
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The development of cancer cachexia is perhaps the most common manifestation of advanced malignant diseases and has been recognized as a poor prognostic sign. The abnormalities associated with the condition include progressive weight loss, anorexia, asthenia, and anemia. The degree of cachexia is inversely correlated with the survival time of the patient and always implies a poor prognosis. Currently there is no established mechanism for cancer cachexia, but the severe metabolic disturbances and marked alterations in carbohydrate, lipid, and protein metabolism in the host finally lead to an increased energy deficiency. Weight loss, the key feature of cachexia, is due to a reduction of food intake, an increase in energy expenditure, or a combination of the two. A variety of changes in nutrient metabolism have been described in patients with cancer cachexia. Patients frequently exhibit a relative glucose intolerance and insulin resistance with increased activity of the Cori cycle. The cancer-bearing state affects protein synthesis and breakdown in different tissues of the body in a different manner. An acute-phase protein response can be presented in a significant proportion of patients with cancer with disease progression. A variety of proinflammatory cytokines appears to play a role in aspects of cachexia and a complex network of cytokines in combination with other factors might be involved. Aside from potential humoral mediators of cachexia, tumor-derived biologically active molecules have been reported recently.
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Food allergy accounts for significant morbidity. The etiology and immune mechanisms of food allergy, however, have remained poorly understood. In this study, we aimed to determine the role of T-cell immunoglobulin-domain and mucin-domain (TIM)-4, a recently identified member of cell surface molecules, in the pathogenesis of intestinal allergy in a murine model. We report that TIM-4 as well as costimulatory molecules were up-regulated in intestinal mucosal dendritic cells by in vitro or in vivo exposure to Staphylococcus enterotoxin B (SEB). SEB-conditioned intestinal dendritic cells loaded with a food macromolecule ovalbumin (OVA) induced potent OVA-specific T-helper (Th)2 lymphocyte responses in vitro and such Th2 responses were inhibited completely by TIM-4 blockade. In vivo exposure to both SEB and OVA resulted in OVA-specific Th2 differentiation and intestinal allergic responses including increased serum immunoglobulin E and Th2 cytokine levels, activation of OVA-specific Th2 cells detected both ex vivo and in situ, and mast cell degranulation. Of importance, in vivo abrogation of TIM-4 or its cognate ligand TIM-1 by using a polyclonal antibody remarkably dampened Th2 differentiation and intestinal allergy. Our study thus identifies TIM-4 as a novel molecule critically required for the development of intestinal allergy.
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Cancer cachexia is associated with weight loss, poor nutritional status, and systemic inflammation. Accurate nutritional support for patients is calculated on resting energy expenditure (REE) measurement or prediction. The present study evaluated the agreement between measured and predicted REE (mREE and pREE, respectively) and the influence of acute phase response (APR) on REE. Thirty-six patients with cancer were divided into weight-stable (WS; weight loss <2%) and weight-losing (WL; weight loss >5%) patients. Measured REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM). The Bland-Altman approach was used to assess the agreement between mREE and pREE from the Harris-Benedict equations (HBE). Blood levels of C-reactive protein were assessed. There was no difference in mREE between groups (WS 1677 +/- 273, WL 1521 +/- 305) even when mREE was adjusted for FFM (WS 1609 +/- 53, WL 1589 +/- 53). In WL patients, FFM-adjusted REE correlated with blood C-reactive protein levels (r = 0.471, P = 0.048). HBEs tend to underestimate REE in both groups. WL and WS patients with cancer had similar REEs but were different in terms of APR. APR could contribute to weight loss through enhancing REE. In a clinical context, HBE was in poor agreement with mREE in both groups.
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Although traditional medicines have been used for thousands of years, for most such medicines neither the active component nor their molecular targets have been very well identified. Curcumin, a yellow component of turmeric or curry powder, however, is an exception. Although inhibitors of cyclooxygenase-2, HER2, tumor necrosis factor, EGFR, Bcr-abl, proteosome, and vascular endothelial cell growth factor have been approved for human use by the United States Food and Drug Administration (FDA), curcumin as a single agent can down-regulate all these targets. Curcumin can also activate apoptosis, down-regulate cell survival gene products, and up-regulate p53, p21, and p27. Although curcumin is poorly absorbed after ingestion, multiple studies have suggested that even low levels of physiologically achievable concentrations of curcumin may be sufficient for its chemopreventive and chemotherapeutic activity. Thus, curcumin regulates multiple targets (multitargeted therapy), which is needed for treatment of most diseases, and it is inexpensive and has been found to be safe in human clinical trials. The present article reviews the key molecular mechanisms of curcumin action and compares this to some of the single-targeted therapies currently available for human cancer.
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New mech-anisms and therapeutic potential of curcumin for colorectal can-cer
  • Villegas I S Sá-Fidalgo
  • Alarcó
Villegas I, Sá-Fidalgo S, Alarcó ?, de la Lastra C. New mech-anisms and therapeutic potential of curcumin for colorectal can-cer. Mol Nutr Food Res 2008;52(9):1040–1061.