oleuropein and Adenocarcinoma

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

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

Crude phenolic extracts (PE) have been obtained from naturally bearing Spanish extra-virgin olive oil (EVOO) showing different polyphenol families such as secoiridoids, phenolic alcohols, lignans, and flavones. EVOO-derived complex phenols (especially from the Arbequina variety olive) have been shown to suppress cell growth of SW480 and HT29 human colon adenocarcinoma cell lines. Inhibition of proliferation by EVOO-PE Arbequina variety extract was accompanied by apoptosis in both colon-cancer-cell lines and a limited G₂M cell-cycle arrest in the case of SW480 cells. The metabolized compounds from EVOO-PE in culture medium and cytoplasm of both cell lines were analyzed using nano-liquid chromatography (nanoLC) coupled with electrospray ionization-time-of-flight-mass spectrometry (ESI-TOF-MS). The results showed many phenolic compounds and their metabolites both in the culture medium as well as in the cytoplasm. The main compounds identified from EVOO-PE were hydroxylated luteolin and decarboxymethyl oleuropein aglycone.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Biotransformation; Cell Proliferation; Chromatography, Liquid; Colonic Neoplasms; Culture Media, Conditioned; Cytoplasm; Decarboxylation; G2 Phase Cell Cycle Checkpoints; HT29 Cells; Humans; Hydroxylation; Iridoid Glucosides; Iridoids; Luteolin; Metabolomics; Nanotechnology; Olive Oil; Phenols; Plant Oils; Pyrans; Spectrometry, Mass, Electrospray Ionization