title: Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation.
abstract: Cancer cells are usually under higher levels of oxidative stress compared to normal cells. We hypothesized that the introduction of additional reactive oxygen species (ROS) or the suppression of antioxidant activity may selectively enhance cancer cell killing by generating oxidative agents through stress overload or stress sensitization. The aim of this work was to test whether hydroxytyrosol (HT), one of the major polyphenolic constituents of extra virgin olive oil, could exert anti-cancer effects on human colon adenocarcinoma cells via its ability to induce apoptosis through ROS generation. HT exhibits preferential anti-proliferative effects on human colon cancer cells (DLD1 cells) but not on normal colon epithelial 1807 cells. HT causes oxidative stress, activates the phosphoinositide 3-kinase/Akt pathway, phosphorylates FOXO3a and then downregulates FOXO3a's target genes. Combined with SOD or catalase treatment, there are different responses in HT-treated DLD1 cells. The results support the hypothesis that the two main species of ROS, superoxide and H2O2, play different roles in cancer cell survival. The present work shows that HT induces apoptotic cell death and mitochondrial dysfunction by generating ROS in colon cancer cells. This research presents important evidence on the in vitro chemopreventive effect of HT and shows that the disruption of the intrinsic redox status promotes cancer cell death.
authors: Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Singapore 117609, Singapore.
authors: Lijuan
authors: L
authors: Sun
authors: Cheng
authors: C
authors: Luo
authors: Jiankang
authors: J
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D015536:Down-Regulation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000069463:Olive Oil; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010938:Plant Oils / Q000008:administration & dosage; D059808:Polyphenols / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D000069463:Olive Oil; D010938:Plant Oils; D059808:Polyphenols; D017382:Reactive Oxygen Species; C005975:3,4-dihydroxyphenylethanol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010626:Phenylethyl Alcohol