title: [10]-Gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells.
abstract: The present study was designed to investigate the molecular mechanisms of [10]-gingerol activity against HCT116 human colon cancer cells. [10]-Gingerol inhibited the proliferation of HCT116 cells by 50% at a concentration of 30 μM, and this inhibition was dose-dependent accompanied by the morphological changes indicative of apoptosis. Furthermore, flow cytometric analysis showed that [10]-gingerol increased DNA in the sub-G1 phase of the cell cycle, and the extent of apoptosis was confirmed by Annexin V and PI double staining. Analysis of the mechanism of these events indicated that [10]-gingerol-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner, which are hallmarks of apoptosis. Moreover, [10]-gingerol-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase (MAPKs) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). This is the first report to demonstrate the cytotoxic effect of [10]-gingerol on human colon cancer cells, as well as the first to describe its possible chemotherapeutic potentials.
authors.affiliation: Department of Foods and Nutrition, College of Natural Sciences, Duksung Women's University, Seoul, 132-714, Republic of Korea.
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Ha Sook
authors.initials: HS
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C007845:gingerol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3