Phenolic extract from oleaster (<i>Olea europaea</i> var. <i>Sylvestris</i>) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway Wafa Zeriouh Abdelhafid Nani Meriem Belarbi Adélie Dumont Charlotte de Rosny Ikram Aboura Fatima Zahra Ghanemi Babar Murtaza Danish Patoli Charles Thomas Lionel Apetoh Cédric Rébé Dominique Delmas Naim Akhtar Khan François Ghiringhelli Mickael Rialland Aziz Hichami 10.1371/journal.pone.0170823 https://plos.figshare.com/articles/dataset/Phenolic_extract_from_oleaster_i_Olea_europaea_i_var_i_Sylvestris_i_leaves_reduces_colon_cancer_growth_and_induces_caspase-dependent_apoptosis_in_colon_cancer_cells_via_the_mitochondrial_apoptotic_pathway/4666651 <div><p>Dietary polyphenols, derived from natural products, have received a great interest for their chemopreventive properties against cancer. In this study, we investigated the effects of phenolic extract of the oleaster leaves (PEOL) on tumor growth in mouse model and on cell death in colon cancer cell lines. We assessed the effect of oleaster leaf infusion on HCT116 (human colon cancer cell line) xenograft growth in athymic nude mice. We observed that oleaster leaf polyphenol-rich infusion limited HCT116 tumor growth in vivo. Investigations of PEOL on two human CRC cell lines showed that PEOL induced apoptosis in HCT116 and HCT8 cells. We demonstrated an activation of caspase-3, -7 and -9 by PEOL and that pre-treatment with the pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), prevented PEOL-induced cell death. We observed an involvement of the mitochondrial pathway in PEOL-induced apoptosis evidenced by reactive oxygen species (ROS) production, a decrease of mitochondrial membrane potential, and cytochrome c release. Increase in intracellular Ca<sup>2+</sup> concentration induced by PEOL represents the early event involved in mitochondrial dysfunction, ROS-induced endoplasmic reticulum (ER) stress and apoptosis induced by PEOL, as ruthenium red, an inhibitor of mitochondrial calcium uptake inhibited apoptotic effect of PEOL, BAPTA/AM inhibited PEOL-induced ROS generation and finally, N-acetyl-L-cysteine reversed ER stress and apoptotic effect of PEOL. These results demonstrate that polyphenols from oleaster leaves might have a strong potential as chemopreventive agent in colorectal cancer.</p></div> 2017-02-17 18:51:43 PEOL-induced cell death colon cancer cell lines colon cancer cells ROS-induced endoplasmic reticulum colon cancer growth Olea europaea var HCT 116 HCT 116 tumor growth ER HCT 8 cells cytochrome c release colon cancer cell line reactive oxygen species PEOL-induced ROS generation mitochondrial apoptotic pathway apoptosi oleaster leaf infusion CRC cell lines BAPTA apoptotic effect oleaster leaf polyphenol-rich infusion mitochondrial calcium uptake