Olive leaf extract impairs mitochondria by pro-oxidant activity in MDA-MB-231 and OVCAR-3 cancer cells

• Published in: Biomedicine & pharmacotherapy 2021-02, Vol.134, p.111139, Article 111139
• Main Authors: Benot-Dominguez, Reyes, Tupone, Maria Grazia, Castelli, Vanessa, d’Angelo, Michele, Benedetti, Elisabetta, Quintiliani, Massimiliano, Cinque, Benedetta, Forte, Iris Maria, Cifone, Maria Grazia, Ippoliti, Rodolfo, Barboni, Barbara, Giordano, Antonio, Cimini, Annamaria
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Female; Humans; Mediterranean diet; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; OLE; Olea - chemistry; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Oxidative Stress - drug effects; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves - chemistry; Reactive Oxygen Species - metabolism; ROS; Signal Transduction; TNBC; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.111139

[Display omitted] •OLE is generally discarded in olive oil industries, but it may be successfully recycled.•OLE inhibits the viability and promotes cell cycle arrest and apoptosis in MDA-MB-231 and OVCAR-3 cells.•OLE increases ROS production and alters the protein levels of oxidative stress pathway related proteins.•OLE compromises mitochondrial function and causes mitochondrial membrane potential (Δψm) loss.•OLE affected cell viability, apoptosis and mitochondrial dysfunction through the activation of ROS. 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.