Olive Leaf Extract Inhibits Breast and Ovarian Cancer Cell Growth and Cell Cycle Progression, Increasing Apoptosis of Tumor Cells

Breast and ovarian cancer are two of the deadliest malignancies among women worldwide. Furthermore, ovarian tumors are generally diagnosed at an already advanced stage and any specific treatment approach has still been individuated to effectively eradicate the disease with a good prognosis. Therefore, new strategies that could help to improve the progression-free survival (PFS) and detect these cancers at an earlier stage are urgently needed. One of these strategies may include the use of herbal-derived active compounds and nutraceuticals, which, since ancient times, have been widely employed for their high therapeutic value in a big range of diseases including infections, neurodegenerative disorders, diabetes and, more recently, cancer.

Following this reasoning, a more exhaustive understanding of how the vegetable fraction of the daily diet may counteract the molecular mechanisms involved in cancers of the female reproductive system, and could help to discover new and better targeted tumor therapies.

Researchers from the University of L’Aquila, Italy, led by Professor Annamaria Cimini at the Life, Health and Environmental Sciences Department, have focused their efforts on the study of the beneficial properties of a discardable plant extract in gynecological cancer disease. Since 2012, Prof. Cimini has also held the position of Adjunct Full Professor at Sbarro Health Research Organization (SHRO), the research organization directed and founded by Prof. Antonio Giordano, M.D., Ph.D., at Temple University.

The group analyzed the antiproliferative activity of a commercial olive leaf extract (OLE) in triple-negative breast and ovarian tumor cells through MTS and Colony formation assays, and identified a dramatic and specific decrease in cell viability in the tumor-treated samples vs. the untreated control groups.

Also, the authors of the study identified a cell cycle arrest and a selective programmed-cell death (apoptosis) upon OLE treatment only within the tumor models, confirming the safety of the extract in normal healthy cells. Pro-apoptotic biomarkers cleaved-Caspase 9 and cleaved PARP were also upregulated exclusively in cancer cells. 

In parallel, mitochondrial functionality was assessed by evaluating both the reactive oxygen species production (ROS) and the mitochondrial membrane potential (MMP). Prof. Cimini’s team observed an overproduction of ROS and mitochondrial impairment with MMP crash as a consequence of the treatment, the reason for which the authors hypothesized that the increase of oxidative stress as the primordial triggering mechanism by which OLE exerts its anticancer effect. Interestingly, pretreatment of tumor cells with the antioxidant N-acetylcysteine (NAC) impeded the antitumor properties of OLE in terms of cell cycle arrest and apoptosis, further supporting the pro-oxidant role of the extract as one of the first steps unleashing the OLE selective antineoplastic properties.

The recent work, with Prof. Cimini as corresponding author, has just been published online in Biomedicine & Pharmacotherapy, a peer-reviewed scientific journal of Elsevier B.V. (ScienceDirect®). This article publication has also been possible through close collaboration with Prof. Giordano’s research group at the Oncology Research Center of Mercogliano (CROM, IRCCS-Pascale Foundation, Naples), and by the funding that one of the first authors, Dr. Benot Dominguez, received from the Rep-eat project, Marie Skłodowska Curie Action (MSCA H2020 G.A. n.713714).

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