1. Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway
- Author
-
Abdelhafid Nani, Naim Akhtar Khan, Ikram Aboura, Adélie Dumont, Meriem Belarbi, Fatima Zahra Ghanemi, Wafa Zeriouh, Danish Patoli, François Ghiringhelli, Aziz Hichami, Babar Murtaza, Lionel Apetoh, Cédric Rébé, Charlotte De Rosny, Dominique Delmas, Mickaël Rialland, Charles Thomas, Produits naturels 'la prona' (Faculté des Sciences de la Nature et de da Vie et Sciences de la Terre et de l’Univers, Université Aboubekr Belkaid), Université Aboubekr Belkaid - University of Belkaïd Abou Bekr [Tlemcen], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL )
- Subjects
0301 basic medicine ,Leaves ,Carcinoma Cells ,lcsh:Medicine ,Apoptosis ,Plant Science ,Mitochondrion ,Endoplasmic Reticulum ,Biochemistry ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,0302 clinical medicine ,Medicine and Health Sciences ,Mitochondrial calcium uptake ,Disease ,lcsh:Science ,Energy-Producing Organelles ,Staining ,chemistry.chemical_classification ,Secretory Pathway ,Multidisciplinary ,Cell Death ,Plant Anatomy ,Cytochrome c ,Cell Staining ,Animal Models ,Mitochondria ,Olive Leaf Extract ,Chemistry ,Oncology ,Experimental Organism Systems ,Cell Processes ,030220 oncology & carcinogenesis ,Physical Sciences ,Cellular Structures and Organelles ,Research Article ,Programmed cell death ,Activation ,Mouse Models ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Bioenergetics ,Biology ,Research and Analysis Methods ,Colorectal-Cancer ,Caspase-Dependent Apoptosis ,03 medical and health sciences ,Model Organisms ,Phenols ,Cytochrome-C ,Colorectal Cancer ,Reactive oxygen species ,P53 ,Cell growth ,Protein ,lcsh:R ,Chemical Compounds ,Biology and Life Sciences ,Cancers and Neoplasms ,Polyphenols ,Cell Biology ,Molecular biology ,030104 developmental biology ,chemistry ,Specimen Preparation and Treatment ,biology.protein ,Calcium ,lcsh:Q - Abstract
Erratum inCorrection: Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway. [PLoS One. 2017]; International audience; 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 Ca2+ 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.
- Published
- 2017