title: Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence             in human glioma cells.
abstract: Therapy-induced senescence, an irreversible growth arrest, in cancer cells             is regarded as a novel functional target that may improve cancer therapy. 20(S)-ginsenoside             Rg3 [20(S)-Rg3], a chemical component extracted from Panax ginseng, has recently             emerged as an effective anticancer medicine with evident antitumor effects and             no observed toxic adverse reactions. We report here that chronic treatment with             20(S)-Rg3 in a sub-lethal concentration induced senescence-like growth arrest             in human glioma cells. Glioma cells treated with 20(S)-Rg3 showed high expression             of senescence-associated β-galactosidase, followed by upregulation of the CDK             inhibitors p21 and p16. Moreover, reactive oxygen species (ROS) generation markedly             increased in 20(S)-Rg3-treated cells compared with control cells. Consistently,             co-incubation with the antioxidant N-acetyl cysteine interfered with 20(S)-Rg3-induced             senescence in glioma cells. In addition, 20(S)-Rg3-induced-activation of Akt was             associated with increased ROS levels, and depletion of Akt partially prevented             20(S)-Rg3-induced ROS generation and senescence induction in glioma cells. Furthermore,             20(S)-Rg3-induced senescence was partially rescued when the p53/p21 pathway was             inactivated. Our data indicate that 20(S)-Rg3 induces senescence-like growth arrest             in human glioma cancer through the Akt and p53/p21-dependent signaling pathways.             This is the first report of a pro-senescent effect of 20(S)-Rg3 in cancer cells.
authors.affiliation: Department of Oriental Medicine, Kyung Hee University College                     of Oriental Medicine, Seoul 130‑701, Republic of Korea.
authors.forename: Seong
authors.initials: S
authors.lastname: Sin
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D036145:Ginsenosides; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C097367:ginsenoside Rg3; D051057:Proto-Oncogene Proteins c-akt