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

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 beta-galactosidase (SA-beta-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. (C) 2011 Wiley-Liss, Inc.