ArticlePublisher preview available

Bitter apricot ethanolic extract induces apoptosis through increasing expression of Bax/Bcl-2 ratio and caspase-3 in PANC-1 pancreatic cancer cells

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Pancreatic cancer is the fourth common cause of cancer death. Surgery and chemotherapy are the common treatment strategies for pancreatic cancer patients; however, the response rate is less than 20% at advanced stages. In recent years, growing interest has been dedicated to natural products. Bitter apricot seeds possess a number of pharmacological properties including antitumor activity and amygdalin from bitter apricot seeds can induce apoptosis. In this study, we investigated the cyto/genotoxic effects of bitter apricot ethanolic extract (BAEE) and amygdalin on human pancreatic cancer PANC-1 and normal epithelial 293/KDR cells. BAEE was assessed using high-performance liquid chromatography for the confirmation of the structure. The biological impacts of BAEE and amygdalin on PANC-1 and 293/KDR cells were evaluated by MTT assay, DAPI staining, AnnexinV/PI and Real-time qPCR analysis. BAEE and amygdalin inhibited cancer cell growth in a dose- and time-dependent manner. DAPI staining and flow cytometric analysis revealed fragmented nuclei and elevated numbers of early and late apoptotic cells, respectively. Also, increased Bax/Bcl-2 ratio and upregulation of caspase-3 further confirmed the occurrence of apoptosis in PANC-1 cells, but not in non-cancerous 293/KDR cells. These results indicate that BAEE could mediate apoptosis induction in cancer cells through a mitochondria dependent pathway. These findings suggest that BAEE functions as a potent pro-apoptotic factor for human pancreatic cancer cells without a significant effect on 293/KDR cells. Though, the potent anti-cancer components of BAEE should be further identified. Moreover, in vivo investigations are required to confirm bitter apricot ethanolic extract’s clinical value as an anti-tumor drug.
This content is subject to copyright. Terms and conditions apply.
Vol.:(0123456789)
1 3
Molecular Biology Reports (2020) 47:1895–1904
https://doi.org/10.1007/s11033-020-05286-w
ORIGINAL ARTICLE
Bitter apricot ethanolic extract induces apoptosis throughincreasing
expression ofBax/Bcl-2 ratio andcaspase-3 inPANC-1 pancreatic
cancer cells
FatemehAamazadeh1,2,3 · AlirezaOstadrahimi1,4 · YaldaRahbarSaadat3,4 · JalehBarar2,5
Received: 20 October 2019 / Accepted: 27 January 2020 / Published online: 5 February 2020
© Springer Nature B.V. 2020
Abstract
Pancreatic cancer is the fourth common cause of cancer death. Surgery and chemotherapy are the common treatment strate-
gies for pancreatic cancer patients; however, the response rate is less than 20% at advanced stages. In recent years, growing
interest has been dedicated to natural products. Bitter apricot seeds possess a number of pharmacological properties includ-
ing antitumor activity and amygdalin from bitter apricot seeds can induce apoptosis. In this study, we investigated the cyto/
genotoxic effects of bitter apricot ethanolic extract (BAEE) and amygdalin on human pancreatic cancer PANC-1 and normal
epithelial 293/KDR cells. BAEE was assessed using high-performance liquid chromatography for the confirmation of the
structure. The biological impacts of BAEE and amygdalin on PANC-1 and 293/KDR cells were evaluated by MTT assay,
DAPI staining, AnnexinV/PI and Real-time qPCR analysis. BAEE and amygdalin inhibited cancer cell growth in a dose- and
time-dependent manner. DAPI staining and flow cytometric analysis revealed fragmented nuclei and elevated numbers of
early and late apoptotic cells, respectively. Also, increased Bax/Bcl-2 ratio and upregulation of caspase-3 further confirmed
the occurrence of apoptosis in PANC-1 cells, but not in non-cancerous 293/KDR cells. These results indicate that BAEE
could mediate apoptosis induction in cancer cells through a mitochondria dependent pathway. These findings suggest that
BAEE functions as a potent pro-apoptotic factor for human pancreatic cancer cells without a significant effect on 293/KDR
cells. Though, the potent anti-cancer components of BAEE should be further identified. Moreover, invivo investigations are
required to confirm bitter apricot ethanolic extract’s clinical value as an anti-tumor drug.
Keywords Pancreatic cancer· Bitter apricot· Amygdalin· Apoptosis
Introduction
Pancreatic cancer is the fourth most common cause of
cancer death worldwide, with a 5-year survival of around
5% [1]. Despite therapeutic advances, pancreatic ductal
Fatemeh Aamazadeh and Yalda Rahbar Saadat have contributed
equally to this work and should be considered as co-first authors.
* Alireza Ostadrahimi
arostadrahimi@gmail.com; ostadrahimi@tbzmed.ac.ir
* Jaleh Barar
jbarar@gmail.com; jbarar@tbzmed.ac.ir
Fatemeh Aamazadeh
amazadeh@yahoo.com
Yalda Rahbar Saadat
yalda.saadat@gmail.com
1 Department ofClinical Nutrition, School ofNutrition
andFood Sciences, Tabriz University ofMedical Science,
Tabriz, Iran
2 Research Center forPharmaceutical Nanotechnology,
Biomedicine Institute, Tabriz University ofMedical
Sciences, Tabriz, Iran
3 Student Research Committee, Tabriz University ofMedical
Science, Tabriz, Iran
4 Nutrition Research Center, Tabriz University ofMedical
Science, Tabriz, Iran
5 Department ofPharmaceutics, Faculty ofPharmacy, Tabriz
University ofMedical Sciences, Tabriz, Iran
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Kernels of Prunus seeds are typically rich in cyanogenic glycoside ''amygdalin'' activation of which occurs via the action of β-glucosidases upon either grinding or chewing of plant tissues followed by intracellular β -glucosidase activation or by gut micro-flora. Several studies have exploited HCN effect on cancer cells to investigate its potency and selectivity (Aamazadeh et al., 2020;Cassiem and De Kock, 2019). Bitter apricot kernel ethanol extract (BAEE) exhibited an antitumor activity with its amygdalin present in bitter apricot seeds found to induce cancer cell apoptosis. ...
... Such cytotoxic mechanism is mediated through mitochondria dependent pathway involving the elevation of Bax/Bcl-2 mRNA expression ratio. Moreover, both BAEE and amygdalin led to an upregulation of caspase 3 that is responsible for apoptotic body formation suggestive that BAEE could be considered as a potent pro-apoptotic agent (Aamazadeh et al., 2020). Another in vitro study investigated the anti-proliferative effect and apoptosis induction of bitter apricot essential oil on psoriasis, which is characterized by the hyperactivity of keratinocyte, mediated by death receptors that include activation of caspases that will lead to DNA-degradation and apoptotic bodies formation (Aamazadeh, F. et al., 2020). ...
... Moreover, both BAEE and amygdalin led to an upregulation of caspase 3 that is responsible for apoptotic body formation suggestive that BAEE could be considered as a potent pro-apoptotic agent (Aamazadeh et al., 2020). Another in vitro study investigated the anti-proliferative effect and apoptosis induction of bitter apricot essential oil on psoriasis, which is characterized by the hyperactivity of keratinocyte, mediated by death receptors that include activation of caspases that will lead to DNA-degradation and apoptotic bodies formation (Aamazadeh, F. et al., 2020). The IC 50 dose for the anti-proliferative effect against on HaCaT cells was at 142 μg/mL after 48 h of treatment mediated via ceasing cell cycle progression at G0/G1 phase, in addition to translocation of the phosphatidylserine from the inner plasma membrane to the cell surface which is a hallmark of early apoptotic cells (Aamazadeh, F. et al., 2020). ...
... The apricot (Prunus armeniaca L.) belongs to the Rosaceae family and is mainly cultivated in the Mediterranean area. The fruit is a source of nutrients and phytochemicals with beneficial antioxidant, antimicrobial, anti-inflammatory, and antimutagenic properties [5][6][7]. In particular, apricot kernels (or Molecules 2022, 27, 7591 2 of 25 seeds) are traditionally used to treat different kind of disorders such as skin disease, hemorrhages, spasms, inflammation, bronchitis, asthma, emphysema, and nausea. ...
... In particular, apricot kernels (or Molecules 2022, 27, 7591 2 of 25 seeds) are traditionally used to treat different kind of disorders such as skin disease, hemorrhages, spasms, inflammation, bronchitis, asthma, emphysema, and nausea. Kernels are a rich source of proteins, carbohydrates, vitamins, fibers, organic acids, phenols, volatile compounds, and lipids and contain the aromatic cyanogenic glycoside amygdalin that has been shown to induce apoptosis and cell cycle arrest in several human cell lines, including prostate, breast, lung, bladder, colon, and rectal cancer cells and keratinocytes [5,[8][9][10][11][12]. In addition, amygdalin exerts an antitumor activity inhibiting metastatic spread through integrin regulation [13]. ...
Article
Full-text available
Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. Methods: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. Results: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. Conclusion: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.
... The apricot (Prunus armeniaca L.) belongs to the Rosaceae family and is mainly cultivated in the Mediterranean area. The fruit is a source of nutrients and phytochemicals with beneficial antioxidant, antimicrobial, anti-inflammatory, and antimutagenic properties [5][6][7]. In particular, apricot kernels (or seeds) are traditionally used to treat different kind of disorders such as skin disease, hemorrhages, spasms, inflammation, bronchitis, asthma, emphysema, and nausea. ...
... In particular, apricot kernels (or seeds) are traditionally used to treat different kind of disorders such as skin disease, hemorrhages, spasms, inflammation, bronchitis, asthma, emphysema, and nausea. Kernels are a rich source of proteins, carbohydrates, vitamins, fibers, organic acids, phenols, volatile compounds, and lipids and contain the aromatic cyanogenic glycoside amygdalin that has been shown to induce apoptosis and cell cycle arrest in several human cell lines, including prostate, breast, lung, bladder, colon, and rectal cancer cells and keratinocytes [5,[8][9][10][11][12]. In addition, amygdalin exerts an antitumor activity inhibiting metastatic spread through integrin regulation [13]. ...
... Consequently, inhibition of mitochondrial electron transport and aerobic ATP generation would critically impair the function of all cells, especially those with a high bioenergetic turnover, such as cancer cells [18]. In the past, amygdalin has been shown to be a potent inhibitor of cell growth in several neoplasms, e.g., bladder, breast, and pancreatic cancer as well as renal cell carcinoma [19][20][21]. Of note, our group has previously demonstrated a substantial inhibition of cell viability in PCa cell lines upon incubation with amygdalin for 24 h or 2 weeks [14]. ...
Article
Full-text available
Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-naïve and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin β1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin β1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin’s value as an antitumor drug.
... In vivo assays of both extracts using Panc02 tumors showed a reduction in tumor volume with a decrease in ki67 expression and an increase in apoptosis-mediated caspase-3 [31]. Moreover, an extract called BAEE was generated using absolute ethanol extraction of Prunus armeniaca L. kernels which was tested in PANC-1 cells showing an IC 50 of 704 µg/mL with an increase in bax/bcl-2 ratio and an overexpression of caspase-3 [32]. ...
Article
Full-text available
The emergence of resistance to pancreatic cancer (PC) current treatment requires the development of new therapeutic strategies. In this context, bioactive molecules from plant extracts have shown excellent properties to improve classical therapy against this type of tumor. This systematic review aims to collect all the in vitro studies related to the antiproliferative activity of isolated plant molecules that support their applicability in PC. A total of 620 articles published in the last 10 years were identified, although only 28 were finally included to meet the inclusion criteria. Our results reflect the most important biomolecules from natural compounds that induce cell death in PC and their essential mechanism of cell death, including apoptosis, pathways activated by the KRAS mutation and cycle cell arrest, among others. These in vitro studies provide an excellent molecule guide showing applications against PC and that should be tested in vivo and in clinical trials to determine their usefulness to reduce PC incidence and to improve the prognosis of these patients. However, natural compounds are isolated in small amounts, which prevents comprehensive drug screening, being necessary the role of organic synthesis for the total synthesis of natural compounds or for the synthesis of their simplified and bioactive analogs.
... [49][50][51] Bcl-2 inhibits Bax activity and prevents it from embedding in the outer mitochondrial membrane, which in turn inhibits caspase-3 activity and exerts an anti-apoptotic effect. [52][53][54] As expected, APL extract markedly increased the expression levels of p-PI3K and p-Akt proteins and activated the PI3K/Akt signaling pathway. Additionally, transcriptional regulation of the PI3K/Akt signaling pathway could regulate the expression of anti-apoptotic protein Bcl-2 and pro-apoptotic proteins Bax, caspase-3, cleaved-caspase-3, thereby reducing cardiomyocyte apoptosis. ...
Article
Full-text available
Purpose: The network pharmacology approach and validation experiment were performed to investigate the potential mechanisms of Agrimonia pilosa Ledeb. (APL) extract against acute myocardial infarction (AMI). Methods: The primary compounds of APL extract were identified by High-Performance Liquid Chromatography (HPLC) analysis. The intersecting targets of active compounds and AMI were determined via network pharmacology analysis. A mouse model of AMI was established by subcutaneous injection of isoproterenol (Iso). Mice were treated with APL extract by intragastric administration. We assessed the effects of APL extract on the electrocardiography (ECG), cardiac representative markers, representative indicators of oxidative stress, pathological changes, and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, as well as apoptosis-related indicators in the mice. Results: Five candidate compounds were identified in APL extract. Enrichment analyses indicated that APL extract could exert myocardial protective effects via the PI3K/Akt pathway. ST segment elevation and increased heart rate were obviously reversed in APL extract groups compared to Iso group. We also detected significant decreases in lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase MB (CK-MB), malondialdehyde (MDA), and reactive oxygen species (ROS), as well as a significant increase in superoxide dismutase activities (SOD) after APL extract treatment. In addition, APL extract markedly decreased the number of apoptotic cardiomyocytes after AMI. In the APL extract groups of AMI mice, there were increased expression levels of p-PI3K, p-Akt, and B-cell lymphoma-2 (Bcl-2) protein, and there were decreases in Bcl-2-associated X (Bax), cysteinyl aspartate-specific proteases-3 (caspase-3), and cleaved-caspase-3 protein expression levels, as well as the Bax/Bcl-2 ratio. Conclusion: APL extract had a protective effect against Iso-induced AMI. APL extract could ameliorate AMI through antioxidant and anti-apoptosis actions which may be associated with the activation of the PI3K/Akt signaling pathway.
... Apoptosis in the PANC-1 cells was confirmed by the upregulation of Bax and caspase-3 and the downregulation of Bcl-2 gene expression, evaluated by real-time PCR. The results indicated that these extracts, as well as amygdalin, induced apoptosis in pancreatic cancer cells through a mitochondrial-dependent pathway [85,86]. [87]. ...
Article
Full-text available
Prunus armeniaca L. (Rosaceae)-syn. Amygdalus armeniaca (L.) Dumort., Armeniaca armeniaca (L.) Huth, Armeniaca vulgaris Lam is commonly known as the apricot tree. The plant is thought to originate from the northern, north-western, and north-eastern provinces of China, although some data show that it may also come from Korea or Japan. The apricot fruit is used medicinally to treat a variety of ailments, including use as an antipyretic, antiseptic, anti-inflammatory, emetic, and ophthalmic remedy. The Chinese and Korean pharmacopeias describe the apricot seed as an herbal medicinal product. Various parts of the apricot plant are used worldwide for their anticancer properties, either as a primary remedy in traditional medicine or as a complementary or alternative medicine. The purpose of this review was to provide comprehensive and up-to-date information on ethnobotanical data, bioactive phytochemicals, anticancer potential, pharmacological applications, and toxicology of the genus Prunus armeniaca, thus providing new perspectives on future research directions. Included data were obtained from online databases such as PubMed/Medline, Google Scholar, Science direct, and Wiley Online Library. Multiple anticancer mechanisms have been identified in in vitro and in vivo studies, the most important mechanisms being apoptosis, antiproliferation, and cytotoxicity. The anticancer properties are probably mediated by the contained bioactive compounds, which can activate various anticancer mechanisms and signaling pathways such as tumor suppressor proteins that reduce the proliferation of tumor cells. Other pharmacological properties resulting from the analysis of experimental studies include neuroprotective, cardioprotective, antioxidant, immunostimulatory, antihyperlipidemic, antibacterial, and antifungal effects. In addition, data were provided on the toxicity of amygdalin, a compound found in apricot kernel seeds, which limits the long-term use of complementary/alternative products derived from P. armeniaca. This updated review showed that bioactive compounds derived from P. armeniaca are promising compounds for future research due to their important pharmacological properties, especially anticancer. A detailed analysis of the chemical structure of these compounds and their cytotoxicity should be carried out in future research. In addition, translational pharmacological studies are required for the correct determination of pharmacologically active doses in humans.
Article
Full-text available
Thiacloprid (THI) is a nicotinic receptor agonist widely used as pesticide in Algeria, however it is susceptible to accumulate in various fruits and vegetables and pouring downstream into food plates and contributes to the development of neurodegenerative diseases. Conversely, several natural compounds are provided with cytoprotective potential and, therefore, are able to act against the harmful effects of toxicants such as pesticides. This study focused on striatum (str) and hippocampus (hipp) mitochondrial toxicity assessment, evaluation of behavioral function and intrinsic apoptosis pathway in rats exposed to THI at low-dose (0.020 mg/kg) for 3 months. In addition, this study examined neuroprotective potential of bitter apricot kernel extract when administered concomitantly with THI at the dose of 50 mg/kg. In current study, assessment of mitochondrial permeability transition pore (mPTP) and swelling, evaluation of mitochondrial redox status, cholinergic function (Ach E) and apoptosis markers (Caspase 9 and 3, Bax and Bcl2, Cytochrome c and cytosolic calcium) were performed in both brain areas, besides behavioral and histopathological examination. The results showed an increase of lipid peroxidation in both of str and hipp with a values of 1,14 ± 0,04 nmol/mg of proteins (pr) and 1,58 ± 0,09 nmol/mg pr. respectively and a significant decrease in GSH (0,09 ± 0,01 mmol/mg pr. in hipp and 0,08±0,01 mmol/mg pr. in str), the results also showed a change in the activity of antioxidants enzymes SOD (16,37±1,09 UI/mg pr. in hipp14,54±1,46 UI/mg pr. in str) , CAT (0,010±0,01 UI/mg pr. in hipp and 0,005±0,004 UI/mg pr. in str), GPx (0,01± 0,001 nmol/mg pr. in both hipp and str) and GST (23,73±1,68 UI/mg pr. in hipp and 17,56± 1,04 UI/mg pr. in str), as well as an abrupt increase in mPTP opening with a value of (0,057±0,005 in str and 0,054±0,005 in hipp) , which leaded to mitochondrial swelling where the level o mitochondrial swelling was (0,016±0,002 in str and 0,106±0,003 in hipp), the swelling was associated also with a high releasing of Cyt-c with a values of (4,48 ± 1,26 µg/ml in str and 5,32 ± 1,08 µg/ml in hipp ) and Ca++( 2,26±0,06 mmol/l in str and 2,32±0,07 mmol/l in hipp) into the cytosol, the results also showed a significant decreasing of Bcl2 (16,4 ± 1,86 ng/mg pr in str and 14,8± 0,82 ng/mg pr in hipp), in the other hand the rates of caspase-9 were (278±14 mAbs/mg pr.) in str and 212 ±24 mAbs/mg pr. in hipp), caspase3 (184± 16mAbs/mg pr.) in str and 250 ±14mAbs/mg pr. in hipp), and BAX (0,926 ng/mg pr in str and 1,189 ng/mg pr in hipp) were increased. The results of this study revealed also a decrease of memorization processes and learning abilities, at the same time a decrease in Ach E activity (14,02± 0,78 nmol/min/mg pr. in str and 22,35± 1,77 nmol/min/mg pr. in hipp) was recorded. Inversely, bitter apricot kernels extract showed higher cytoprotective potential against THI neurotoxicity, since mitochondrial redox homeostasis and membrane integrity were recovered, cognitive impairment and brain tissue damage were also prevented. In conclusion, THI induced mitochondrial disorders, triggered apoptosis signaling pathway and impaired cognitive functions which were prevented by bitter apricot kernels extract when associated with this pesticide.
Article
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change >2.0 and [Formula: see text] < 0.05 were acquired from the cDNA microarray analysis. The results of qRT-PCR further confirmed that the differentially-expressed level of the NF[Formula: see text]B-1 gene was most obviously enhanced in lung cancer cells treated with amygdalin. The results of immunofluorescence staining, Western blotting and siRNA knockdown indicated that amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via enhancing the expression of NF[Formula: see text]B-1 and inactivating NF[Formula: see text]B signaling cascade and further changing the expressions of proteins (Bax, Bcl-2, cytochrome C, caspase 9, caspase 3 and PARP) related to apoptosis, which were further checked by in vivo study of the lung cancer cell xenograft mice model accompanying with immunohistochemical staining and TUNEL staining. Our results indicated that amygdalin might be a potential activator of NF[Formula: see text]B-1, which sheds more light on the molecular mechanism of anticancer effects of amygdalin. These results highlighted amygdalin as a potential therapeutic anticancer agent, which warrants its development as a therapy for lung cancer.
Article
We investigated using histochemistry and immunohistochemistry ovarian damage caused by nonylphenol (NP) and the protective effect of melatonin treatment of NP induced ovarian damage. We used 21 female rats divided randomly into three groups: control, NP and melatonin + NP. Histopathological examination of the ovaries, and counting and classification of follicles were performed using Masson's trichrome staining. Expression of anti-Mullerian hormone (AMH), Bax, Bcl-2 and caspase-3 was detected in the ovaries using immunohistochemistry. Melatonin had an ameliorative effect on NP induced follicular atresia and absence of corpora lutea. More follicles were observed in the ovaries of animals treated with melatonin prior to treatment with NP. AMH immunoreactivity was significantly lower in the NP group than in the melatonin + NP group. NP increased immunostaining for Bax, Bcl-2 and caspase-3. Melatonin significantly reduced the increased expression of Bax, Bcl-2 and caspase-3 due to NP exposure. We found that pretreatment with melatonin is beneficial for protecting the ovaries from damage by NP.
Article
Full-text available
In spite of several studies that have shown the cytotoxic effects of amygdalin on the different cancer cell lines, however, the chemopreventive potential of amygdalin on the breast cancer cell line is not completely understood. We investigated the effect of amygdalin on the cell death and the level of pro-apoptotic Bax protein and anti-apoptotic Bcl-2 protein in SK-BR-3 human breast cancer cell line. The cell viability of SK-BR-3 cells was evaluated by MTT assay in different concentration of amygdalin. The level of Bax and Bcl-2 in SK-BR-3 cells were measured by western blot analysis. For statistical analysis, One-way ANOVA was used for the comparison of Bax and Bcl-2 protein level and percent of cell viability between groups. The molecular docking studies of amygdalin within the Bcl-2 (PDB ID: 4LVT) and HER2 (PDB ID: 3RCD) active site, were performed using AutoDock 4.2.5. Amygdalin induced a significant reduction of cell viability in SK-BR-3 after 24-h treatment in a dose-dependent manner. Also, amygdalin causes an increase in pro-apoptotic Bax protein and a decrease in anti-apoptotic Bcl-2 protein expression in the SK-BR-3 cells. Molecular docking studies showed that amygdalin interacts with the active site amino acids of Bcl-2 and HER2 through hydrogen bonding and some hydrophobic interactions. Amygdalin can induce apoptotic death in SK-BR-3 cells by increasing pro-apoptotic Bax protein and decreasing anti-apoptotic Bcl-2 protein expression. The results suggest that amygdalin may be a valuable candidate for the treatment of breast cancer, especially in HER2 positive cells.
Article
Full-text available
Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.
Article
Full-text available
Background Colorectal malignant neoplasms is one of the leading causes of death in both men and women in the developed world and the incidence has recently increased markedly in South Africa. Studies have highlighted the beneficial effects of Amygdalin, a cyanogenic compound found in both peach and apricot kernels, in its ability to suppress the development of colon cancer. The focus of this study was to investigate the potential anti-proliferative properties of various apricot and peach kernels extractions from South Africa and China and to monitor alterations in cell cycle kinetics in colon cancer cells. Methods Studies were conducted on HT-29 colon cancer cells. The interactive role of three different kernel extractions on the modulation of cell proliferation, apoptosis and cell cycle progression was monitored over 24, 48 and 72 h periods. Results After 24 h, all extracts of the South African apricot kernels had a dose related bi-phasic proliferative effect on the HT-29 cells. It stimulated cell proliferation at the lowest and highest concentrations while at 500 μg/mL it inhibited cell proliferation. In contrast, after 72 h, the low concentration inhibited cell proliferation while the 500 μg/mL extracts stimulated cell proliferation. Morphological changes were observed in cells incubated with Chinese kernel extracts after 24 h and South African kernel treatment (1000 μg/mL) after 72 h. A possible intra-S-phase block after 24 and 48 h exposure to South African hydrophilic kernel extracts was observed. This transient block that is more concerned with tolerating and accommodating damage during replication rather than repairing it, could explain the initial anti-proliferative effects observed after 24 h exposure to the various Chinese kernel extract concentrations. Conclusion Abrogation of the block by exhaustion of the cyanide production, most likely allowed the cells to resume the cell cycle and continue into mitosis, whereas low ATP levels caused by the presence of amygdalin in the kernels, can also cause the induction of pycnosis or necrosis. These results highlight the possible mechanisms of growth inhibition by amygdalin containing extracts and may contribute towards the development of dietary anti-cancer therapies.
Article
Full-text available
Impaired apoptosis plays a central role in cancer development and limits the efficacy of conventional cytotoxic therapies. Deepening understanding of how opposing factions of the BCL-2 protein family switch on apoptosis and of their structures has driven development of a new class of cancer drugs that targets various pro-survival members by mimicking their natural inhibitors, the BH3-only proteins. These ‘BH3 mimetic’ drugs seem destined to become powerful new weapons in the arsenal against cancer. Successful clinical trials of venetoclax/ABT-199, a specific inhibitor of BCL-2, have led to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies. Furthermore, encouraging preclinical studies of BH3 mimetics that target other BCL-2 pro-survival members, particularly MCL-1, offer promise for cancers resistant to venetoclax. This review sketches the impact of the BCL-2 family on cancer development and therapy, describes how interactions of family members trigger apoptosis and discusses the potential of BH3 mimetic drugs to advance cancer therapy.
Article
Full-text available
Amygdalin contents of the seeds, endocarps, and mesocarps from three peach cultivars (i.e., Stone Peach, Hikawa Hakuho, and Bakhyang) were measured at three stages of fruit development (stone-hardening, fruit enlargement, and ripening). The peach samples were dried and defatted with a Soxhlet apparatus, reflux extracted with methanol, and analyzed using reverse phase high-performance liquid chromatography. During all fruit development stages, the amygdalin contents in the seeds were higher than those in the endocarps and mesocarps. The amygdalin contents of the Stone Peach were comparatively higher than the Hikawa Hakuho and Bakhyang (P<0.05). Further, the amygdalin contents during ripening were very low or not detected. Overall, the amygdalin contents of the three peach cultivar samples (seed, endocarp, and mesocarp) increased until the fruit enlargement stage and either remained constant or decreased during ripening. © Copyright 2017 by The Korean Society of Food Science and Nutrition. All rights Reserved.
Article
Full-text available
Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.
Article
Full-text available
Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.
Article
Ethnopharmacological relevance: Bidens pilosa L, belonging to the family of Acanthaceae, has been used as an anticancer medicine in folk in China. In our preliminary experiments, the petroleum ether extract from B. pilosa showed good cytotoxic activity to human lung cancer A549 cell. However, to date, it's lack of the further study on antitumor effect, mechanism and active substances composition of the petroleum ether extract of B. pilosa. Aim of the study: The study aimed to evaluate the anti-lung cancer efficacy of the petroleum ether extract from B. pilosa (PEEBP) in vitro and in vivo, explore the possible anticancer mechanisms, and further disclose the chemical composition of the extract. Materials and methods: B. pilosa was extracted with 75% ethanol (v/v), followed by extracted with petroleum ether to obtain the objective fraction. Antiproliferation effect of the petroleum ether extract in HepG2, A549, CNE and B16 cells was evaluated by MTT assay. The in vivo anticancer effect was examined by A549 cells nude mice xenograft tumor model. The possible effect mechanism was studied by western blot assay. The chemical constituents of the extract was analyzed by GC-MS. Results: The petroleum ether extract showed favorable antiproliferation activity against the four human cancer cell lines, especially for A549 cells with an IC50of 49.11 ± 2.72μg/mL. The extract inhibited the growth of A549 cell in mice with the inhibitory rates of 24.76%, 35.85% and 53.07% for 90, 180 and 360mg/kg oral dosages, respectively. The B. pilosa extract could significantly down-regulate the expression of apoptosis-related protein Bcl-2 and up-regulate the protein expression of Bax and Caspase-3. 138 compounds were identified by GC-MS in the extract and the main chemical components were triterpenes, including 4,22-cholestadien-3-one (4.82%), stigmasterol (4.56%), friedelan-3-one (3.28%), etc. Conclusion: The PEEBP is abundant of triterpenes and has significant anti-tumor activities against human A549 cells in vitro and in vivo, indicating it a potential anticancer agent.
Article
Promising results from different studies on the effect of probiotics in cancer prevention and therapy have so far been reported. However, the molecular mechanism of the interaction of probiotics with cancer cells is yet to be fully understood. In the present study, Leuconostoc mesenteroides was isolated from traditional dairy products, and its probiotic characteristics were determined. HT-29 cells were treated with conditioned-medium of designated bacteria and the cell apoptosis was studied at cellular and molecular level using DAPI staining, flow cytometry, DNA ladder assays, and real-time quantitative-PCR (q-PCR). Based on our findings, L. mesenteroides promoted apoptosis in colon cancer cell line by upregulation of MAPK1, Bax, and caspase 3, and downregulation of AKT, NF-κB, Bcl-XL expressions and some key oncomicroRNAs such as miRNA-21 and miRNA-200b significantly (p≤0.03). The results indicated the likelihood of the examined probiotic as an alternative or complementary treatment modality in signaling-targeted cancer therapy.
Article
Background: In the Netherlands, like in many other European countries, pancreatic cancer mortality was found to be systematically higher than the incidence. This suggests that there is an underestimation of the reported incidence of pancreatic cancer. Aim: We aimed to study the incidence of pancreatic cancer in the Rotterdam area and to compare this with the national level. Methods: This study is embedded in the Rotterdam Study (RS), an ongoing population-based prospective cohort study of people aged 45 years and above, enrolled between 1989 till 2006. Details on incident pancreatic cancer cases were available until 2013. Age-specific incidence rates were calculated and compared with data available in the Netherlands Cancer Registry. Results: At baseline 14,922 participants were at risk of developing pancreatic cancer. Median follow-up time was 16.4 person years per person. In total, 113 participants developed pancreatic cancer. Rates increased with age with an incidence rate of 109.9 (95% confidence interval [CI]; 85.7-138.8) per 100,000 person years for people older than 75. This is higher than the currently reported 55.9-89.2 per 100,000 person year. Of the 113 cases identified in the RS, only 67.3% was reported as pancreatic cancer in the Netherlands Cancer Registry. Cases that was not registered were significantly older and had significantly poorer survival. Conclusion: The incidence of pancreatic cancer, as registered by the Netherlands Cancer Registry, is an underestimation. Patients, not registered by the cancer registry, have a significantly poorer survival. Consequently, we probably overestimate the already poor survival of pancreatic cancer.