oleuropein has been researched along with Breast-Neoplasms* in 19 studies
1 review(s) available for oleuropein and Breast-Neoplasms
1 trial(s) available for oleuropein and Breast-Neoplasms
18 other study(ies) available for oleuropein and Breast-Neoplasms
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Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion via Induction of Autophagy in ER-Positive Breast Cancer Cell Lines (MCF7 and T47D).
Hydroxytyrosol (HT) and oleuropein (OL), the most abundant of the phenolic compounds in olives, have anticancer properties against breast cancer (BC). However, little attention has been paid to the mechanism of HT or OL in BC cells. The objective of this study was to identify the underlying molecular mechanisms of these compounds. ER-positive BC MCF7 and T47D cells were treated with HT and OL in combination with hepatocyte growth factor (HGF), rapamycin (Rapa, an agonist of autophagy) or 3-methyladenine (3-MA, an inhibitor of autophagy). Cell viability, metastasis capability and autophagy-related proteins were evaluated by wound healing assays, Transwell assays and Western blot. HT and OL reduced the cell viability of MCF-7 and T47D cells in a dose-dependent manner. Both cells were more sensitive to HT than OL. In addition, Rapa significantly inhibited HGF-induced migration and invasion, indicating that metastases of both BC cells could be inhibited by suppression of autophagy. Moreover, HT and OL significantly blocked HGF- or 3-MA-induced cell migration and invasion by reversing LC3II/LC3I and Beclin-1 downregulation and p62 upregulation. These findings revealed that HT and OL could suppress migration and invasion by activating autophagy in ER-positive BC cells, which might be a promising therapeutic strategy. Topics: Autophagy; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; Iridoid Glucosides; MCF-7 Cells; Phenylethyl Alcohol | 2021 |
Oleuropein is a natural inhibitor of PAI-1-mediated proliferation in human ER-/PR- breast cancer cells.
Elevated expression of PAI-1 has been widely linked with adverse outcomes in a variety of human cancers, such as breast, gastric and ovarian cancers, rendering PAI-1 a prognostic biomarker. As a result, several chemical inhibitors are currently being developed against PAI-1; however, the clinical setting where they might confer survival benefits has not yet been elucidated.. RNA sequencing data analysis from the TCGA/GTEx cancer portals (n = 3607 samples). In silico molecular docking analyses to predict functional macromolecule interactions. ER-/PR- (MDA-MB-231) and ER+/PR+ (MCF-7) breast cancer cell lines implemented to assess the effect of oleuropein as a natural inhibitor of PAI-1-mediated oncogenic proliferation.. We show that high PAI-1 levels inversely correlate with ER and PR expressions in a wide panel of estrogen/progesterone-responsive human malignancies. By implementing an in silico molecular docking analysis, we identify oleuropein, a phenolic component of olive oil, as a potent PAI-1-binding molecule displaying increased affinity compared to the other olive oil constituents. We demonstrate that EVOO or oleuropein treatment alone may act as a natural PAI-1 inhibitor by incrementally destabilising PAI-1 levels selectively in ER-/PR- breast cancer cells, accompanied by downstream caspase activation and cell growth inhibition. In contrast, ER+/PR+ breast cancer cells, where PAI-1 expression is absent or low, do not adequately respond to treatment.. Our study demonstrates an inverse correlation between PAI-1 and ESR1/PGR levels, as well as overall patient survival in estrogen/progesterone-responsive human tumours. With a focus on breast cancer, our data identify oleuropein as a natural PAI-1 inhibitor and suggest that oleuropein-mediated PAI-1 destabilisation may confer clinical benefit only in ER-/PR- tumours. Topics: Breast Neoplasms; Cell Proliferation; Female; Humans; Iridoid Glucosides; Molecular Docking Simulation; Plasminogen Activator Inhibitor 1; Receptors, Estrogen; Receptors, Progesterone | 2021 |
The effect of oleuropein on apoptotic pathway regulators in breast cancer cells.
In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this end, we examined the effect of oleuropein on two breast cancer cell lines (MCF7 and MDA-MB-231). Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner, while it increased the apoptosis in MCF7 and MDA-MB-231 cells. In the presence of oleuropein, the expression levels of miR-125b, miR-16, miR-34a, p53, p21, and TNFRS10B increased, while that of bcl-2, mcl1, miR-221, miR-29a and miR-21 decreased. The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression of pro-apoptotic genes and tumor suppressor miRNAs, but also decreasing the expression of anti-apoptotic genes and oncomiR. Consequently, oleuropein can be regarded as a suitable herbal medication for cancer therapy. Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Computational Biology; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Iridoid Glucosides; MicroRNAs; Signal Transduction | 2020 |
PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.
Phosphatase PTP1B has become a therapeutic target for the treatment of type 2-diabetes, whereas recent studies have revealed that PTP1B plays a pivotal role in pathophysiology and development of breast cancer. Oleuropein is a natural, phenolic compound with anticancer activity. The aim of this study was to address the question whether PTP1B constitutes a target for oleuropein in breast cancer MCF-7 cells. The cellular MCF-7 breast cancer model was used in the study. The experiments were performed using cellular viability tests, Elisa assays, immunoprecipitation, flow cytometry analyses and computer modelling. Herein, we evidenced that the reduced activity of phosphatase PTP1B after treatment with oleuropein is strictly correlated with decreased MCF-7 cellular viability and cell cycle arrest. These results provide new insight into further research on oleuropein and possible role of the compound in adjuvant treatment of breast cancer. Topics: Adenocarcinoma; Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Cell Survival; Humans; Iridoid Glucosides; Iridoids; MCF-7 Cells; Molecular Dynamics Simulation; Protein Tyrosine Phosphatase, Non-Receptor Type 1 | 2019 |
Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo.
Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies.. The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved.. The research team designed in vivo (animal) and in vitro (cell culture) studies.. The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia).. The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1).. The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (control group)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia.. The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting.. The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappa Β, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used.. The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts. Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Female; Humans; Iridoid Glucosides; Iridoids; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Recurrence, Local | 2019 |
Oleuropein induces apoptosis via abrogating NF-κB activation cascade in estrogen receptor-negative breast cancer cells.
Oleuropein is one of the most abundant phenolic compounds found in olives. Epidemiological studies have indicated that an increasing intake of olive oil can significantly reduce the risk of breast cancer. However, the potential effect(s) of oleuropein on estrogen receptor (ER)-negative breast cancer is not fully understood. This study aims to understand the anticancer effects and underlying mechanism(s) of oleuropein on ER-negative breast cancer cells in vitro. The effect of oleuropein on the viability of breast cancer cell lines was examined by mitochondrial dye-uptake assay, apoptosis by flow cytometric analysis, nuclear factor-κB (NF-κB) activation by DNA binding/reporter assays and protein expression by Western blot analysis. In the present report, thiazolyl blue tetrazolium bromide assay results indicated that oleuropein inhibited the viability of breast cancer cells, and its effects were more pronounced on MDA-MB-231 as compared with MCF-7 cells. It was further found that oleuropein increased the level of reactive oxygen species and also significantly inhibited cellular migration and invasion. In addition, the activation of NF-κB was abrogated as demonstrated by Western blot analysis, NF-κB-DNA binding, and luciferase assays. Overall, the data indicates that oleuropein can induce substantial apoptosis via modulating NF-κB activation cascade in breast cancer cells. Topics: Apoptosis; Breast Neoplasms; Female; Humans; Iridoid Glucosides; Iridoids; MCF-7 Cells; NF-kappa B; Receptors, Estrogen | 2019 |
Oleuropein inhibits migration ability through suppression of epithelial-mesenchymal transition and synergistically enhances doxorubicin-mediated apoptosis in MCF-7 cells.
Distinct metastasis is one of the main causes of breast cancer (BC)-related mortality and epithelial-mesenchymal transition (EMT) is a primary step in metastasis dissemination. On the other hand, doxorubicin (DOX) is an effective chemotherapeutic agent against BC; unfortunately, its clinical use is limited by dose-dependent side effects. Therefore, extensive efforts have been dedicated to suppressing metastasis of BC and also to overcome DOX side effects together with keeping its antitumor efficacy. Studies supported the role of oleuropein (OLEU) in reducing DOX-induced side effects besides its antitumor actions. In this study, the antimigratory effect of OLEU was assessed and real-time PCR (RT-PCR) was used to detect OLEU effect on the expression level of EMT markers, in MCF-7 cells. The cytotoxic effect of OLEU and DOX was assessed by MTT assay, whereas the ratio of apoptosis was investigated by flow cytometry. The results showed that migration ability of MCF-7 cells remarkably decreased in OLEU treated group and RT-PCR results showed that OLEU may exert its antimigratory action by suppressing EMT through downregulation of sirtuin1 (SIRT1). Also, the results indicated that both OLEU and DOX were cytotoxic to MCF-7 cells, whereas DOX-OLEU cotreatment led to additive cytotoxicity and apoptosis rate. This study provides evidence regarding the suppressive role of OLEU on MCF-7 cells migration ability through suppression of EMT, and for the first time, it was proposed that SIRT1 downregulation can be involved in the OLEU antimigratory effect. Also, the findings demonstrated that OLEU can reduce DOX-induced side effects by reducing its effective dose. Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Breast Neoplasms; Cell Movement; Down-Regulation; Doxorubicin; Drug Synergism; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Iridoid Glucosides; Iridoids; MCF-7 Cells; Neoplasm Invasiveness; Signal Transduction; Sirtuin 1 | 2019 |
Downregulation of HDAC2 and HDAC3 via oleuropein as a potent prevention and therapeutic agent in MCF-7 breast cancer cells.
Breast cancer is the most common malignancy in the world with the highest rate of morbidity and mortality. Due to the several side effects of chemotherapy and radiotherapy, recent studies have focused on the use of herbal medicines. Epidemiological reports have shown the inverse relationship between breast cancer risk and intake of olive. Oleuropein (OLE) is a polyphenolic compound in virgin olive oil with antineoplastic properties and it is well tolerated by humans. Recent reports have shown that OLE has effects on the control of cancer by modulating epigenetics, such as histone deacetylase (HDAC) inhibition. However, the epigenetic mechanisms of OLE anticancer properties are yet to be properly investigated. Therefore, this study aimed to determine the therapeutic effects of OLE through the modulation of histone deacetylase 2 (HDAC2) and histone deacetylase 3 (HDAC3) expression in breast cancer cell line. MCF-7 cells were tested with and without OLE, and also the cell viability, apoptosis, and migration were examined. HDAC2 and HDAC3 expression genes were assessed by quantitative real-time polymerase chain reaction. It was found that OLE decreased the expression of both HDAC2 and HDAC3 (P < 0.05), induced apoptosis and retarded cell migration and cell invasion in a dose-dependent manner (P < 0.05). These results showed that OLE is a potential therapeutic and preventive agent for breast cancer. Topics: Antineoplastic Agents; Breast Neoplasms; Cell Movement; Cell Survival; Female; Histone Deacetylase 2; Histone Deacetylases; Humans; Iridoid Glucosides; Iridoids; MCF-7 Cells | 2019 |
Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy.
Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs. Topics: Analysis of Variance; Apoptosis; Breast Neoplasms; Cell Movement; Cell Survival; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Iridoid Glucosides; Iridoids; MCF-7 Cells; MicroRNAs; Neoplasm Invasiveness | 2018 |
Oleuropein and hydroxytyrosol activate GPER/ GPR30-dependent pathways leading to apoptosis of ER-negative SKBR3 breast cancer cells.
We have previously demonstrated that oleuropein (OL) and hydroxytyrosol (HT) reduce 17β-estradiol-mediated proliferation in MCF-7 breast cancer (BC) cells without affecting the classical genomic action of estrogen receptor (ER), but activating instead the ERK1/2 pathway. Here, we hypothesized that this inhibition could be mediated by a G-protein-coupled receptor named GPER/GPR30. Using the ER-negative and GPER-positive SKBR3 BC cells as experimental model, we investigated the effects of OL and HT on GPER-mediated activation of downstream pathways.. Docking simulations and ligand-binding studies evidenced that OL and HT are able to bind GPER. MTT cell proliferation assays revealed that both phenols reduced SKBR3 cell growth; this effect was abolished silencing GPER. Focusing on OL and HT GPER-mediated pathways, using Western blot analysis we showed a sustained ERK1/2 activation triggering an intrinsic apoptotic pathway.. Showing that OL and HT work as GPER inverse agonists in ER-negative and GPER-positive SKBR3 BC cells, we provide novel insights into the potential of these two molecules as tools in the therapy of this subtype of BC. Topics: Apoptosis; Breast Neoplasms; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Iridoid Glucosides; Iridoids; Phenylethyl Alcohol; Receptors, Estrogen; Receptors, G-Protein-Coupled; Signal Transduction; Tumor Cells, Cultured | 2014 |
Oleuropein induces apoptosis via the p53 pathway in breast cancer cells.
Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis.. p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells.. Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2.. Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway. Topics: Antihypertensive Agents; bcl-2-Associated X Protein; Blotting, Western; Breast Neoplasms; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Iridoid Glucosides; Iridoids; Proto-Oncogene Proteins c-bcl-2; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured; Tumor Suppressor Protein p53 | 2014 |
A metabolite-profiling approach to assess the uptake and metabolism of phenolic compounds from olive leaves in SKBR3 cells by HPLC-ESI-QTOF-MS.
Olive leaves, an easily available natural low-cost material, constitute a source of extracts with significant antitumor activity that inhibits cell proliferation in several breast-cancer-cell models. In this work, a metabolite-profiling approach has been used to assess the uptake and metabolism of phenolic compounds from an olive-leaf extract in the breast-cancer-cell line SKBR3 to evaluate the compound or compounds responsible for the cytotoxic activity. For this, the extract was firstly characterized quantitatively by high-performance liquid chromatography coupled to electrospray ionization-quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS). Then, SKBR3 cells were incubated with 200 μg/mL of the olive-leaf extract at different times (15 min, 1, 2, 24, and 48 h). A metabolite-profiling approach based on HPLC-ESI-QTOF-MS was used to determine the intracellular phenolic compounds, enabling the identification of 16 intact phenolic compounds from the extract and four metabolites derived from these compounds in the cell cytoplasm. The major compounds found within the cells were oleuropein, luteolin-7-O-glucoside and its metabolites luteolin aglycone and methyl-luteolin glucoside, as well as apigenin, and verbascoside. Neither hydroxytyrosol nor any of its metabolites were found within the cells at any incubation time. It is proposed that the major compounds responsible for the cytotoxic activity of the olive-leaf extract in SKBR3 cells are oleuropein and the flavones luteolin and apigenin, since these compounds showed high uptake and their antitumor activity has been previously reported. Topics: Apigenin; Breast Neoplasms; Carcinoma; Cell Line, Tumor; Chromatography, High Pressure Liquid; Cytoplasm; Female; Flavones; Glucosides; Humans; Iridoid Glucosides; Iridoids; Luteolin; Olea; Phenols; Plant Extracts; Plant Leaves; Pyrans; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry | 2013 |
Identification of the factors responsible for the in vitro pro-oxidant and cytotoxic activities of the olive polyphenols oleuropein and hydroxytyrosol.
The olive polyphenols oleuropein and hydroxytyrosol were reported recently to produce extracellular hydrogen peroxide (H2O2) under standard culture conditions. The precise factors responsible for this production and the conditions promoting or retarding it are critical for the interpretation of the in vitro results. In this study, a systematic evaluation of the components of the most commonly used culture media revealed that sodium bicarbonate is the defining cause for the production of H2O2 by these polyphenols. The produced H2O2 caused extensive oxidative DNA damage and significant decrease in cell viability of cancer (MDA-MB-231) and normal (MCF-10A, STO) cells alike. Sodium pyruvate and the antioxidant N-acetyl cysteine (NAC) totally reversed these effects. Therefore, we conclusively identified the culture conditions that promote H2O2 production by these polyphenols, producing artifacts that may be misinterpreted as a specific anticancer activity. Our findings raise considerable questions regarding the use of culture media with sodium bicarbonate or sodium pyruvate as components, for the in vitro study of these and possibly other plant polyphenols. Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Culture Media; Female; Humans; Hydrogen Peroxide; Iridoid Glucosides; Iridoids; Mice; Olea; Oxidants; Oxidative Stress; Phenylethyl Alcohol; Plant Extracts; Plant Oils; Pyrans; Reactive Oxygen Species | 2013 |
Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells.
Breast cancer constitutes a major health problem for women worldwide. However, its incidence varies between populations and geographical locations. These variations could be diet-related, since there are several carcinogenic compounds in the modern diet, while natural products contain various anti-cancer elements. Several lines of evidence indicate that, in addition to their clear preventive effect, these compounds could also be used as therapeutic agents. In the present report we have shown that oleuropein, a pharmacologically safe natural product of olive leaf, has potent anti-breast cancer properties. Indeed, oleuropein exhibits specific cytotoxicity against breast cancer cells, with higher effect on the basal-like MDA-MB-231 cells than on the luminal MCF-7 cells. This effect is mediated through the induction of apoptosis via the mitochondrial pathway. Moreover, oleuropein inhibits cell proliferation by delaying the cell cycle at S phase and up-regulated the cyclin-dependent inhibitor p21. Furthermore, oleuropein inhibited the anti-apoptosis and pro-proliferation protein NF-κB and its main oncogenic target cyclin D1. This inhibition could explain the great effect of oleuropein on cell proliferation and cell death of breast cancer cells. Therefore, oleuropein warrants further investigations to prove its utility in preventing/treating breast cancer, especially the less-responsive basal-like type. Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Cycle; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Electrophoresis, Polyacrylamide Gel; Female; Flow Cytometry; Humans; Iridoid Glucosides; Iridoids; MCF-7 Cells; Mitochondria; NF-kappa B; Olive Oil; Plant Oils; Pyrans; Receptors, Estrogen; Up-Regulation | 2013 |
Oleuropein induces anti-metastatic effects in breast cancer.
Breast cancer causes death due to distant metastases in which tumor cells produce matrix metalloproteinase (MMP) enzymes which facilitate invasion. Oleuropein, the main olive oil polyphenol, has anti-proliferative effects. This study aimed to investigate the effect of oleuropein on the metastatic and anti-metastatic gene expression in the MDA human breast cancer cell line. We evaluated the MMPs and TIMPs gene expression by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in treated and untreated cells. This study demonstrated that OL may induce anti-metastatic effects on human breast cancer cells. We found that TIMP1,-3, and -4 were over-expressed after all periods of incubation in treated cancer cells compared to untreated cells, while MMP2 and MMP9 genes were down-regulated, at least initially. Treatment of breast cancer cells with oleuropein could help in prevention of cancer metastasis by increasing the TIMPs and suppressing the MMPs gene expressions. Topics: Analysis of Variance; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Iridoid Glucosides; Iridoids; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Metastasis; Pyrans; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-3; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Up-Regulation | 2012 |
Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation.
The growth of many breast tumors is stimulated by estradiol (E2), which activates a classic mechanism of regulation of gene expression and signal transduction pathways inducing cell proliferation. Polyphenols of natural origin with chemical similarity to estrogen have been shown to interfere with tumor cell proliferation. The aim of this study was to investigate whether hydroxytyrosol (HT) and oleuropein (OL), two polyphenols contained in extra-virgin olive oil, can affect breast cancer cell proliferation interfering with E2-induced molecular mechanisms. Both HT and OL inhibited proliferation of MCF-7 breast cancer cells. Luciferase gene reporter experiments, using a construct containing estrogen responsive elements able to bind estrogen receptor alpha (ERalpha) and the study of the effects of HT or OL on ERalpha expression, demonstrated that HT and OL are not involved in ERalpha-mediated regulation of gene expression. However, further experiments pointed out that both OL and HT determined a clear inhibition of E2-dependent activation of extracellular regulated kinase1/2 belonging to the mitogen activating protein kinase family. Our study demonstrated that HT and OL can have a chemo-preventive role in breast cancer cell proliferation through the inhibition of estrogen-dependent rapid signals involved in uncontrolled tumor cell growth. Topics: Anticarcinogenic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Estradiol; Estrogen Receptor alpha; Female; Humans; Iridoid Glucosides; Iridoids; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phenylethyl Alcohol; Protein Kinase Inhibitors; Pyrans; Transcriptional Activation | 2010 |
Qualitative screening of phenolic compounds in olive leaf extracts by hyphenated liquid chromatography and preliminary evaluation of cytotoxic activity against human breast cancer cells.
In this work, high-performance liquid chromatography (HPLC) coupled to electrospray time-of-flight mass spectrometry (ESI-TOF-MS) and electrospray ion trap multiple-stage tandem mass spectrometry (ESI-IT-MS(2)) has been applied to screen phenolic compounds in olive leaf extracts. The use of a small particle size C18 column (1.8 micro) provided great resolution and made separation of a lot of isomers possible. The structural characterization was based on accurate mass data obtained by ESI-TOF-MS, and the nature of fragmentation ions were further confirmed by ESI-IT-MS(2) when possible. In addition, we employed tetrazolium salt (MTT)-based assays to assess the effects of olive leaf extracts on the growth of human tumor-derived cells. Upon this approach, we achieved an accurate profile of olive leaf phenolics along with the identification of several important isomers of secoiridoids and flavonoids. This will allow a better understanding of the complete composition of olive-leaf-bioactive compounds as well as their involvement in Olea europaea L. biochemical pathways. Importantly, olive leaf extracts exhibited dose-dependent inhibitory effects on the metabolic status (cell viability) of three breast cancer models in vitro. Since the tumoricidal activity of the extracts should be mainly attributed to the identified olive leaf phenolics, these findings warrant further investigation at the structure-function molecular level to definitely establish the anticancer value of these phytochemicals. Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Carcinoma; Cell Survival; Chromatography, High Pressure Liquid; Cinnamates; Female; Flavonoids; Humans; Iridoid Glucosides; Iridoids; Olea; Phenols; Plant Leaves; Pyrans; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry | 2010 |
Olive oil's bitter principle reverses acquired autoresistance to trastuzumab (Herceptin) in HER2-overexpressing breast cancer cells.
A low incidence of breast cancer in the Mediterranean basin suggests that a high consumption of Extra Virgin Olive Oil (EVOO) might confer this benefit. While the anti-HER2 oncogene effects of the main omega-9 fatty acid present in EVOO triacylglycerols (i.e., oleic acid) have been recently described, the anti-breast cancer activities of EVOO non-glyceridic constituents--which consist of at least 30 phenolic compounds--remained to be evaluated.. Semi-preparative HPLC was used to isolate EVOO polyphenols (i.e., tyrosol, hydroxytyrosol, oleuropein). Both the anti-proliferative and the pro-apoptotic effects of EVOO phenolics were evaluated by using MTT-based quantification of metabolically viable cells and ELISA-based detection of histone-associated DNA fragments, respectively. The nature of the interaction between oleuropein aglycone and the anti-HER2 monoclonal antibody trastuzumab (Herceptin) was mathematically evaluated by the dose-oriented isobologram technique. HER2-specific ELISAs were employed to quantitatively assess both the basal cleavage of the HER2 extracellular domain (ECD) and the expression level of total HER2. The activation status of HER2 was evaluated by immunoblotting procedures using a monoclonal antibody specifically recognizing the tyrosine phosphorylated (Phosphor-Tyr1248) form of HER2.. Among EVOO polyphenols tested, oleuropein aglycone was the most potent EVOO phenolic in decreasing breast cancer cell viability. HER2 gene-amplified SKBR3 cells were ~5-times more sensitive to oleuropein aglycone than HER2-negative MCF-7 cells. Retroviral infection of the HER2 oncogene in MCF-7 cells resulted in a "SKBR3-assimilated" phenotype of hypersensitivity to oleuropein aglycone. An up to 50-fold increase in the efficacy of trastuzumab occurred in the presence of oleuropein aglycone. A preclinical model of acquired autoresistance to trastuzumab (SKBR3/Tzb100 cells) completely recovered trastuzumab sensitivity (> 1,000-fold sensitization) when co-cultured in the presence of oleuropein aglycone. Indeed, the nature of the interaction between oleuropein aglycone and trastuzumab was found to be strongly synergistic in Tzb-resistant SKBR3/Tzb100 cells. Mechanistically, oleuropein aglycone treatment significantly reduced HER2 ECD cleavage and subsequent HER2 auto-phosphorylation, while it dramatically enhanced Tzb-induced down-regulation of HER2 expression.. Olive oil's bitter principle (i.e., oleuropein aglycone) is among the first examples of how selected nutrients from an EVOO-rich "Mediterranean diet" directly regulate HER2-driven breast cancer disease. Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Cell Line, Tumor; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Iridoid Glucosides; Iridoids; Olive Oil; Plant Extracts; Plant Oils; Pyrans; Trastuzumab | 2007 |