Olive leaf extract impairs mitochondria by pro-oxidant activity in MDA-MB-231 and OVCAR-3 cancer cells
Autor: | Benedetta Cinque, Michele d'Angelo, Annamaria Cimini, Massimiliano Quintiliani, Reyes Benot-Dominguez, Iris Maria Forte, Antonio Giordano, Rodolfo Ippoliti, Elisabetta Benedetti, Maria Grazia Cifone, Maria Grazia Tupone, Vanessa Castelli, Barbara Barboni |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Mitochondrial ROS Mediterranean diet Mitochondria OLE Ovarian cancer ROS TNBC OLE Mediterranean diet TNBCO varian cancer Mitochondria ROS Apoptosis Triple Negative Breast Neoplasms RM1-950 Mitochondrion medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Olea medicine Humans Viability assay Cell Proliferation Pharmacology Membrane Potential Mitochondrial Ovarian Neoplasms Cell growth Chemistry Plant Extracts General Medicine Cell Cycle Checkpoints Molecular biology Antineoplastic Agents Phytogenic 3. Good health Plant Leaves Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Female Therapeutics. Pharmacology Reactive Oxygen Species Intracellular Oxidative stress Signal Transduction |
Zdroj: | Biomedicine & Pharmacotherapy, Vol 134, Iss, Pp 111139-(2021) |
Popis: | Breast and ovarian cancers are the leading and fifth reason for tumor death among females, respectively. Recently, many studies demonstrated antiproliferative activities of natural aliments in cancer. In this study, we investigated the antitumor potential of Olive Leaf Extract (OLE) in triple-negative breast and ovarian cancer cells. A HPLC/DAD analysis on OLE has been performed to assess the total polyphenolics and other secondary metabolites content. HCEpiC, MDA-MB-231, and OVCAR-3 cell lines were used. MTS, Cytofluorimetric, Western Blot analysis were performed to analyze cell viability, cell proliferation, apoptosis, and oxidative stress. Fluorimetric and IncuCyte® analyses were carried out to evaluate apoptosis and mitochondrial function. We confirmed that OLE, containing a quantity of oleuropein of 87 % of the total extract, shows anti-proliferative and pro-apoptotic activity on MDA-MB-231 cells. For the first time, our results indicate that OLE inhibits OVCAR-3 cell viability inducing cell cycle arrest, and it also increases apoptotic cell death up-regulating the protein level of cleaved-PARP and caspase 9. Moreover, our data show that OLE treatment causes a significant decrease in mitochondrial functionality, paralleled by a reduction of mitochondrial membrane potential. Interestingly, OLE increased the level of intracellular and mitochondrial reactive oxygen species (ROS) together with a decreased activity of ROS scavenging enzymes, confirming oxidative stress in both models. Our data demonstrate that mitochondrial ROS generation represented the primary mechanism of OLE antitumor activity, as pretreatment with antioxidant N-acetylcysteine prevented OLE-induced cell cycle arrest and apoptosis. |
Databáze: | OpenAIRE |
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