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Abstract

Cancer is a multifaceted disease characterized by deregulated epigenetic, genetic and metabolic signals which affect cellular metabolism and apoptosis. Breast cancer is regarded to be the most common malignancy in the women worldwide. The side effects of chemo-drugs such as non-selectivity, toxicity and resistance urge scientists to find more potent and safer drugs. Natural products from plants provide an extensive array of chemical scaffolds with biosafety profiles, and safer health effects. Curcuma, a genus of family Zingiberaceae, comprises of about 110 species natively distributed as well as cultivated in South Asia, China, Australia, Sri Lanka, West Indies, and Peru. This plant is used as a remarkable pharmacological remedy to prevent and cure various pathological disorders including cancer. The chemical constituents of this plant, terpenoids and betaketones, specifically act as the anti-breast cancer agents. Curcuma, the marvel of nature, can be regarded as panacea due to its versatile molecular targets and spacious therapeutic window. Various investigations on the essential oils and dry rhizome conclude that the chemical constituents of this plant e.g., curcumin, germacrone, furanodienone, bisdethoxycurcumin, demethoxycurcumin, curcumol, and aromatic turmerone are responsible for its anti-breast cancer potential. These compounds, either as single compound or in combinations with other drugs, are known to arrest cell cycle and induce apoptosis in breast cancer cells by modulating various signaling cascades including NF-κB, STAT3, PI3k/Akt/mTOR and MAPK. This book chapter intends to comprehend the biological and pharmacological mode of action of Curcuma-derived anti-breast cancer compounds in order to update the researchers and scientific community about the pharmaceutical potential of plants belonging to this genus.

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Curcumolhas been reported to possess antitumor activity. However, its effect and mechanisms against tumor metastasis are still unclear. This study is to investigate the inhibitory effect of curcumol on breast cancer cell metastasis and elucidate the underlying molecular mechanisms. Our results showed that noncytotoxicity was caused by curcumol within 10 to 40 µg/mL in MDA-MB-231 and 4T1 cells for 24 hours, whereas sustained treatment with curcumol for 14 days significantly suppressed the clonogenic activity of cells. Importantly, curcumol at noncytotoxic concentrations suppressed the migration ability of both MDA-MB-231 and 4T1 cells. Moreover, curcumol suppressed the migration and invasion of MDA-MB-231 cells in the Boyden chamber migration and invasion assay and inhibited the adhesion of MDA-MB-231 cells onto the matrigel. Further investigations revealed that curcumol decreased the enzyme activity and protein expression of matrix metalloproteinase (MMP-9) in MDA-MB-231 cells. Moreover, curcumol inhibited the activation of c-Jun N-terminal kinase (JNK) 1/2 and Akt (Ser473). Meanwhile, it also inhibited the nuclear translocation and transcriptional activity of nuclear factor κB (NF-κB). Furthermore, JNK inhibitor SP600125 and Akt (Ser473) inhibitor LY294002 enhanced the inhibition of curcumol on NF-κB p65 nuclear translocation. Finally, supplementation with SP600125, LY294002, or NF-κB inhibitor Ammonium pyrrolidinedithiocarbamate (PDTC) significantly enhanced the inhibitory effect of curcumol on MMP-9 expression and cell migration, invasion, and adhesion in MDA-MB-231 cells. Our findings provide evidence for the suppression of breast cancer cell metastasis by curcumol and suggest that the inhibition of MMP-9 via JNK1/2 and Akt (Ser473)-dependent NF-κB signaling pathways may be the underlying mechanisms.
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Chemoresistance is a major cause of recurrence and poor prognosis in triple-negative breast cancer (TNBC) patients. The essential oil of Rhizoma Curcumae has been recently reported to enhance the chemosensitivity of cancer cells. However, few reports have systematically illuminated the mechanism. Curcumol is the major component of the essential oil of Rhizoma Curcumae. Therefore, we wondered whether curcumol combined with chemotherapy could increase the anticancer effects. In the present study, we evaluated the anticancer effects of doxorubicin and curcumol alone or in combination by a series of growth proliferation and apoptosis assays in TNBC cells. Our results showed that curcumol enhanced the sensitivity of MDA-MB-231 cells to doxorubicin in vitro and in vivo. Through miRNA-seq, we found that miR-181b-2-3p was involved in the curcumol-mediated promotion of doxorubicin-sensitivity in both parental and doxorubicin-resistant MDA-MB-231 (MDA-MB-231/ADR) cells. Further study showed that miR-181b-2-3p suppressed ABCC3 expression by targeting its 3'UTR. More importantly, we identified that overexpression of miR-181b-2-3p sensitized MDA-MB-231/ADR cells to doxorubicin by inhibiting the drug efflux transporter ABCC3. Furthermore, we found that NFAT1 could be activated by curcumol. In addition, ChIP assay results revealed that NFAT1 could directly bind to the promoter region of miR-181b-2-3p. Finally, using PDX models, we identified that curcumol could enhance sensitivity to doxorubicin to suppress tumor growth by the miR-181b-2-3p-ABCC3 axis in vivo. Taken together, our study provides novel mechanistic evidence for curcumol-mediated sensitization to doxorubicin in TNBC, and it highlights the potential therapeutic usefulness of curcumol as an adjunct drug in TNBC patients with doxorubicin-resistance.
Article
Rhizomes of Curcuma caesia are traditionally used to treat cancer in India. The aim is to isolate chemical constituents from C. caesia rhizomes through bioassay-guided fractionation. The extract, hexanes and chloroform fractions showed effect on MCF-7 and MDA-MB-231cells in cell viability assay. The chromatographic separation afforded germacrone (1), zerumbone (2), furanodienone (3), curzerenone (4), curcumenol (5), zederone (6), curcumenone (7), dehydrocurdione (8) from hexanes fraction and curcuminol G (9), curcuzederone (10), (1S, 10S), (4S,5S)-germacrone-1 (10), 4-diepoxide (11), wenyujinin B (12), alismoxide (13), aerugidiol (14), zedoarolide B (15), zedoalactone B (16), zedoarondiol (17), isozedoarondiol (18) from chloroform fraction. This is first report of compounds 2, 9–13, 15–18 from C. caesia. The study demonstrated compounds 1–4 and 10 are the bioactive compounds. The effect of curcuzederone (10) on MDA-MB-231 cell migration showed significant inhibition in scratch and Transwell migration assays. The results revealed that curcuzederone could be a promising drug to treat cancer.
Article
Curcumin (diferuloylmethane), an orange‑yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of Curcuma longa. For centuries, curcumin has been used in medicinal preparations and as a food colorant. In recent years, extensive in vitro and in vivo studies have suggested that curcumin possesses activity against cancer, viral infection, arthritis, amyloid aggregation, oxidation and inflammation. Curcumin exerts anticancer effects primarily by activating apoptotic pathways in cancer cells and inhibiting pro‑cancer processes, including inflammation, angiogenesis and metastasis. Curcumin targets numerous signaling pathways associated with cancer therapy, including pathways mediated by p53, Ras, phosphatidylinositol‑3‑kinase, protein kinase B, Wnt‑β catenin and mammalian target of rapamycin. Clinical studies have demonstrated that curcumin alone or combined with other drugs exhibits promising anticancer activity in patients with breast cancer without adverse effects. In the present review, the chemistry and bioavailability of curcumin and its molecular targets in breast cancer are discussed. Future research directions are discussed to further understand this promising natural product.
Article
This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high‐quality cancer registry data, the basis for planning and implementing evidence‐based cancer control programs, are not available in most low‐ and middle‐income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1‐31. © 2018 American Cancer Society
Article
Curcumin is the major constituent of turmeric (Curcuma longa). Turmeric has been widely used as a spice in foods and for therapeutic applications such as anti-inflammatory, antihyperlipidemic, and antimicrobial activities. Turmeric and curcumin are nonmutagenic and nongenotoxic. Oral use of turmeric and curcumin did not have reproductive toxicity in animals at certain doses. Studies on human did not show toxic effects, and curcumin was safe at the dose of 6 g/day orally for 4–7 weeks. However, some adverse effects such as gastrointestinal upsets may occur. Moreover, oral bioavailable formulations of curcumin were safe for human at the dose of 500 mg two times in a day for 30 days, but there are still few trials and more studies are needed specially on nanoformulations and it should be discussed in a separate article. In addition, curcumin is known as a generally recognized as safe substance. This review discusses the safety and toxicity of turmeric and curcumin in medicine. Turmeric and curcumin are nontoxic for human especially in oral administration. Turmeric and curcumin are also safe in animals. They are nonmutagenic and are safe in pregnancy in animals but more studies in human are needed.
Article
Curcuma aromatica was used as an oriental Traditional Chinese Medicine (TCM), and it is mainly distributed in Guangxi, China. In this study, 10 batches of C. aromatica were collected from different origins in Guangxi. The fingerprints were established by HPLC technique to investigate the quality stability of C. aromatica. Spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica was assessed by similarity analysis (SA), gray relational analysis (GRA) and multiple linear regression analysis (MLRA). From the results, the similarity values between each batch of C. aromatica and reference fingerprint were more than 0.880, indicated the good quality stability of the 10 batches of C. aromatica. 20 common peaks were selected as the fingerprints to evaluate the quality and hypolipidemic effect of C. aromatica. The results of spectrum-effect relationship showed that peaks 10, 18, 13, 15 and 17 in the fingerprints were closely related to hypolipidemic effect. This study successfully established the spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica, which provided methods for quality control and more effectively studies on bioactive compounds of C. aromatica. It could also provide a new simple and effective method for utilizing the fingerprints to optimize the Chinese prescription and develop TCM.
Article
Limonene (C₁₀H₁₆) and bisabolene (C₁₅H₂₄) are both naturally occurring terpenes in plants. Depending on the number of C₅ units, limonene and bisabolene are recognized as representative monoterpenes and sesquiterpenes, respectively. Limonene and bisabolene are important pharmaceutical and nutraceutical products used in the prevention and treatment of cancer and many other diseases. In addition, they can be used as starting materials to produce a range of commercially valuable products, such as pharmaceuticals, nutraceuticals, cosmetics, and biofuels. The low abundance or yield of limonene and bisabolene in plants renders their isolation from plant sources non-economically viable. Isolation of limonene and bisabolene from plants also suffers from low efficiency and often requires harsh reaction conditions, prolonged reaction times, and expensive equipment cost. Recently, the rapid developments in metabolic engineering of microbes provide a promising alternative route for producing these plant natural products. Therefore, producing limonene and bisabolene by engineering microbial cells into microbial factories is becoming an attractive alternative approach that can overcome the bottlenecks, making it more sustainable, environmentally friendly and economically competitive. Here, we reviewed the status of metabolic engineering of microbes that produce limonene and bisabolene including microbial hosts, key enzymes, metabolic pathways and engineering of limonene/bisabolene biosynthesis. Furthermore, key challenges and future perspectives were discussed.
Article
Plants belonging to the genus Curcuma are gaining importance globally as one of the significant ingredients in food and traditional medicines. Apart from being considered as nutritionally rich food products, interest in medicinal properties of Curcuma species has increased due to the discovery of novel bioactive compounds possessing wide bioactivities such as antioxidant, antiviral, antimicrobial, and anti-inflammation activities. This article summarizes the literature pertaining to the nutritional values, bioactive compounds, as well as the biological activities of 16 edible Curcuma species. Additionally, the bioavailability, cytotoxicity, and allied health benefits of these species are also discussed and highlighted. The brief information provided in this review will open future perspectives for investigations related to their possible use as functional foods and in pharmaceutical applications.
Article
Eight new sesquiterpenoids (1–8), two new diterpenoids (9 and 10), and 17 known sesqui- and diterpenoids (11–27) were isolated from the radix of Curcuma aromatica. Among these compounds, 1 is an unprecedented guaiane with unique cyclopropane and furan functionalities, and 9 is the first atisane diterpenoid isolated from a Curcuma species. Their 2D and 3D structures were established using HRESIMS and spectroscopic methods, including ECD and IECD data. The antioxidant activities of compounds 1–27 were evaluated based on their ability to protect PC12 cells against H2O2-induced damage, with 1, 2, 5–8, 11, 12, 14, 16, 18, and 19 exhibiting notable antioxidant effects on oxidative injury induced by H2O2.
Article
Objective: To estimate the contents of curcuminoids in two samples of Curcuma karnatakensis collected from different localities. Methods: Quantification of curcuminoids was estimated by ultra-high performance liquid chromatography-mass spectrometry/selected reaction monitoring (UHPLC-MS/SRM) method in two samples of C. karnatakensis for the first time. Fine powder of rhizomatous rootstocks of two plant samples collected from different habitats were served as Samples A and B. The MS used for the metabolite analysis is a Vantage TSQ triple stage quadrupole MS equipped with heated electrospray ionization. The MS is coupled with an Agilent 1290 infinity UHPLC system. A stock solution of curcuminoid standard was prepared by dissolving 5 mg of standard in 1 mL of methanol. Seven different concentrations of standard (0.15-10 ng on column) were injected for the UHPLC-MS/SRM analysis. Separations were performed using a C-18 column with a flow rate of 0.2 mL/minute. Results: Contents of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were found to be varied in two samples and lowest than any other species of Curcuma studied. Variation in the contents may be due to their different habitats in which they are growing. Conclusion: The present attempt of analyzing the contents of curcuminoids in this endemic taxon for the first time will provide the basis for further pharmacological analysis to authenticate the efficacy of these active principles as the curcuminoids are known for varied pharmacological activities.
Article
Objective: To estimate the contents of curcuminoids in two samples of Curcuma karnatakensis collected from different localities.Methods: Quantification of curcuminoids was estimated by ultra-high performance liquid chromatography-mass spectrometry/selected reaction monitoring (UHPLC-MS/SRM) method in two samples of C. karnatakensis for the first time. Fine powder of rhizomatous rootstocks of two plant samples collected from different habitats were served as Samples A and B. The MS used for the metabolite analysis is a Vantage TSQ triple stage quadrupole MS equipped with heated electrospray ionization. The MS is coupled with an Agilent 1290 infinity UHPLC system. A stock solution of curcuminoid standard was prepared by dissolving 5 mg of standard in 1 mL of methanol. Seven different concentrations of standard (0.15-10 ng on column) were injected for the UHPLC-MS/SRM analysis. Separations were performed using a C-18 column with a flow rate of 0.2 mL/minute.Results: Contents of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were found to be varied in two samples and lowest than any other species of Curcuma studied. Variation in the contents may be due to their different habitats in which they are growing.Conclusion: The present attempt of analyzing the contents of curcuminoids in this endemic taxon for the first time will provide the basis for further pharmacological analysis to authenticate the efficacy of these active principles as the curcuminoids are known for varied pharmacological activities.
Article
Background: While the anti-inflammatory and anticancer potential of curcumin, which is derived from turmeric (Curcuma longa), has been studied extensively, very little is known about Calebin A, another novel compound from the same source. Purpose: To determine whether Calebin A exhibits anti-inflammatory and anticancer potential. Methods: We examined the anti-inflammatory potential of Calebin A by DNA binding of NF-κB. Anticancer properties of Calebin were determined by MTT and FACS analysis and NF-κB regulated expression of proteins was assessed by western blotting. Results: Calebin A suppressed NF-κB activation induced by various stimuli. This inhibition of NF-κB activation was mediated through the suppression of direct binding of NF-κB/p65 to the DNA. This inhibitory effect was reversed by a reducing agent, and mutation of the Cys38 of p65 to serine abolished the effect of Calebin A on this binding. Suppression of NF-κB activation by Calebin A resulted in the down-regulation of the expression of proteins involved in tumor cell survival, proliferation, inflammation, and metastasis. Furthermore, Calebin A inhibited proliferation and induced apoptosis in a wide variety of tumor cells, as examined by various assays. It enhanced apoptosis induced by chemotherapeutic agents. Conclusion: Our results demonstrate that Calebin A inhibits NF-κB activation pathway through interaction with p65 and potentiates apoptosis in cancer cells; thus, it has potential in the treatment of cancer. However, further in vivo studies are warranted to define its anti-inflammatory and anticancer potential.
Article
Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170].Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings.
Article
Curcumol, a major volatile component in Rhizoma Curcumae, exhibited potent anti-metastatic effect on breast cancer cells. However, its molecular mechanism remains poorly understood. In this study, we employed a 2-DE based proteomics to investigate the cellular targets of curcumol in MDA-MB-231 cells, and identified 10 differentially expressed proteins. Moreover, Gene Ontology analysis revealed that those proteins mainly get involved in 9 types of cellular components, 7 different biological processes and 9 kinds of molecular functions, and 35 pathways (p < 0.05) were enriched by KEGG pathway analysis. Specially, eEF1A1, a well-characterized actin binding protein, draws our attention. Curcumol decreased eEF1A1 expression at both mRNA and protein levels. EEF1A1 expression was shown to be correlated with the invasiveness of cancer cells. Importantly, overexpression of eEF1A1 significantly reversed the inhibition of curcumol on the invasion and adhesion of MDA-MB-231 cells (p < 0.05). Together, our data suggest that eEF1A1 may be a potential molecular target underlying the anti-metastatic effect of curcumol.
Article
The β-diketone scaffold is a key intermediate of COX-2 inhibitors, a type of non-steroidal anti-inflammatory agents of the coxib family which are also proven to have excellent anticancer potential at the preclinical stage of research. Moreover, it is present in the family of natural products named curcuminoids. Both natural products and their synthetic analogs possess interesting antibacterial, neuroprotective and anticancer properties. Coordination compounds of curcuminoids with platinum-group metals as potential anticancer agents are a hot topic of current research as to our knowledge most scientific articles on this topic were published in the last 5 years. Structurally simpler diketones, e.g. acetylacetone derivatives are also employed in the design of novel metal-based agents. Most notably, the first non-platinum metal-based anticancer compound which entered clinical trials was budotitane, cis-diethoxy(1-phenylbutane-1,3-dionato)titanium(IV). Recently, several studies of platinum-group coordination and organometallic compounds, their biological evaluation and mode-of-action studies were published in high impact journals in the field of inorganic and medicinal chemistry.
Article
A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line ( A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when ceUs are incubated together with the extract of Curcuma longa , the potential bioactive compounds in the extract should selectively combine with the cells , then the ceU-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 ceUs , which wiil produce interference in the blank solution. In this paper , by using ceUs digestion and multi-step centrifugation and transfer strategy , the interference problem has been solved. FinaUy , using the developed method , three ceU-binding compounds were screened out and were identified as bisdemethoxycurcumin , demethoxycurcumin , and cur- cumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner waU of ceU culture flask , which wiil to be an effective complementary method for current target ceU extraction-chemical profiling technology.
Article
The study was conducted to investigate the effects of dietary administrations of four nutraceuticals in dogs. Seventy four dogs were enrolled in the trials, 24 healthy dogs were fed with a control diet (CT) and the experimental groups received for 60 days the same diet supplemented with nutraceuticals, namely Echinacea angustifolia (EA, 0.10 mg/kg live weight as echinacoside; 14 dogs), Vaccinium myrtillus (VM, 0.20 mg/kg live weight as anthocyanidin, 13 dogs), Curcuma longa (CL, 6.60 mg/kg live weight as curcumin, 18 dogs with arthrosis), and Sylibum marianum (SM, 1.5 mg/kg live weight as sylibin, 8 dogs with hepatopathy). Dogs were weighted at the beginning of study and blood samples were collected at the beginning (T0) and at the end (T60) of the study. VM significantly down regulated TNF, CXCL8, NFKB1 and PTGS2 and decreased plasma ceruloplasmin (CuCp). The activity of EA was evidenced by the significant decrease of TNF and NFKB1 expression and CuCp levels and by the increase of plasma Zn. Administration of CL caused a significant decrease of CuCp and increase of Zn and a down regulation of TNF, CXCL8, NFKB1 and PTGS2, corroborating the anti-inflammatory action of curcuminoids. After 60 days of treatment with SM, plasma ALT/GPT activity was reduced and paraoxonase was increased, supporting the antioxidant activity of silymarin, also confirmed by the significant up regulation of SOD2. Results indicated that nutraceutical administrations in dogs can be an interesting approach to modulate immune response in order to improve health condition of animals.
Article
Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. Linked articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
Article
Estrogen receptor (ER)α-positive breast cancer cells regulate the expression of estrogen-responsive genes, which are involved in cell proliferation, differentiation, and cell cycle progression. Clinically, the inhibition of ERα-mediated gene expression in breast cancer cells has long been considered an effective way to prevent the development and progression of cancer. Germacrone, a terpenoid compound isolated from Rhizoma curcuma, has been known to have antitumor activity in various human cancer cell lines. However, the mechanism by which germacrone inhibits the proliferation of breast cancer cells is still unclear. Here, we demonstrated that germacrone inhibits ERα-mediated gene expression at the transcriptional level in MCF-7 cells. Germacrone inhibits the recruitment of ERα to the estrogen response element on chromatin and consequently compromises the binding of switch/sucrose non-fermentable chromatin remodeling complex and RNA polymerase II to target gene promoter, thereby inhibiting the estrogen-induced chromatin accessibility. In addition, germacrone efficiently potentiates the antitumor activity of methotrexate and 5-fluorouracil. Our results not only provide substantial molecular mechanism of germacrone on ERα-mediated signaling in breast cancer cells but also demonstrate the benefits of germacrone as a combination therapy with other drugs for the treatment of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
Article
In recent years, several drugs have been developed deriving from traditional products and current drug research is actively investigating the possible therapeutic roles of many Ayruvedic and Traditional Indian medicinal therapies. Among those being investigated is Turmeric. Its most important active ingredient is curcuminoids. Curcuminoids are phenolic compounds commonly used as a spice, pigment and additive also utilized as a therapeutic agent used in several foods. Comprehensive research over the last century has revealed several important functions of curcuminoids. Various preclinical cell culture and animals studies suggest that curcuminoids have extensive biological activity as an antioxidant, neuroprotective, antitumor, anti-inflammatory, anti-acidogenic, radioprotective and arthritis. Different clinical trials also suggest a potential therapeutic role for curcuminoids in numerous chronic diseases such as colon cancer, lung cancer, breast cancer, inflammatory bowel diseases. The aim of this review is to summarize the chemistry, analog, metal complex, formulations of curcuminoids and their biological activities.