title: Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces senescence-like terminal S-phase arrest in human hepatoma and breast cancer cells.
abstract: Senescence is a permanent growth arrest and has been implicated as an efficient anti-carcinogenesis mechanism. The purpose of this study was designed to test the hypothesis that penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a naturally occurring polyphonolic gallotannin compound, might induce this type of permanent growth arrest in cancer cells. Our results show, for the first time, that PGG-induced senescence-like S-phase arrest in HepG2, Huh-7 human hepatoma cells, and SKBr3 human breast cancer cells at sublethal doses, judged by cellular morphological changes, increased senescence-associated β-galactosidase (SA-β-gal) activity, together with loss of proliferative capacity after being released from the treatment. This senescence-like response was mediated by intracellular ROS generation, but was not attributed to p53 Ser15 phosphorylative activation and was uncoupled from the p21cip1 axis, which has been shown to mediate Pten loss-induced cellular senescence or oncogene-driven senescence. The findings of the present study implicate a novel mechanism of PGG action to induce an atypical cellular senescence, adding to its promise as a potential chemopreventive agent.
authors.affiliation: Division of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing.
authors.forename: Shutao
authors.initials: S
authors.lastname: Yin
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Dong
authors.forename: Jinhua
authors.initials: J
authors.lastname: Li
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047348:Hydrolyzable Tannins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C435084:pentagalloylglucose