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