Antiproliferative Activity of Antioxidants-Rich Extracts from <i>Olea europaea</i> L. Leaves and Oil Against Six Cancerous Human Cell Lines

The present work aims to study the cytotoxic effect of the methanolic extract of leaves and oil of three olive cultivars: Manzanillo, Picual and Koronieki. Against six cancer cell lines, namely MCF-7 and MDA (breast cancer), HepG2 (liver cancer), PC3 (prostate cancer), Caco-2 (colon cancer), and A549 (lung cancer) using the MTT method. The results obtained showed that Manzanillo leaf methanolic extract (LMME) and Manzanillo oil (OMME) gave the highest cytotoxicity with the lowest IC50 against Caco2 and A549 cell lines. To explain this result, the mechanism of action was studied at the chemical, cellular and molecular levels. The chemical composition analysis of LMME and OMME was performed by GC-MAS. Furthermore, phytochemical analysis was performed. In addition to cell cycle analysis and apoptosis induction, the gene expression of three apoptotic genes was measured. The total phenolic contents (TPC) and total flavonoid contents (TFC) of (LMME) were greater than that of (OMME). Both LMME and OMME had arrested cell cycle at G1 phase for each of Caco2 and A549 cells. LMME and OMME induce up regulation of Casp3 and BAX genes and down regulation of Bcl-2 gene. These results indicated that, LMME and OMME had anti-proliferation effect against Caco2 and A549 cells through induction of apoptosis pathway. Further detailed studies are needed to examine the effect of each fraction of whole extract.