Penta-1,2,3,4,6-O-galloyl-β-D-glucose induces p53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo

Hongbo Hu, Hyo Jeong Lee, Cheng Jiang, Jinhui Zhang, Lei Wang, Yan Zhao, Qiu Xiang, Eun Ok Lee, Sung Hoon Kim, Junxuan Lü

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) is a naturally occurringg allotannin from some Oriental herbs. Several cell culture studies suggested a potential for PGG as a novel agent for the chemoprevention and treatment of cancer. Here, we investigated the cell death signaling mechanisms induced by PGG in human prostate cancer cells of different p53 functional status. We observed the induction of G1- and S-phase arrests and caspase-mediated apoptosis in the androgen-dependent human LNCaP cells, which express wild-type p53, and in the androgen-independent, p53-mutant DU145 cells. In LNCaP cells, caspase-mediated apoptosis induction by PGG was associated with and mediated in major part by activation of p53 as established through small interfering RNA knockdown and dominant-negative mutant approaches. Intracellular reactive oxygen species production by PGG was found to be crucial for these molecular and cellular actions. In DU145 cells, which harbor constitutively active signal transducer and activator of transcription 3 (STAT3), caspase-mediated apoptosis induction by PGG was associated with an inhibition of STAT3 Tyr705 phosphorylation and the down-regulation of STAT3 transcriptional targets Bcl-XL and Mcl-1. Overexpression of Bcl-XL or knockdown of its bindingpartner Bak attenuated apoptosis induction. Furthermore, we provide, for the first time, in vivo data that PGG significantly inhibited DU145 xenograft growth in an athymic nude mouse model in association with an inhibition of pSTAT3. Our data support PGG as a multitargeting agent for chemoprevention and therapy of prostate cancer by activatingthe p53 tumor suppressor pathway and by inhibiting STAT3 oncogenic signaling.

Original languageEnglish (US)
Pages (from-to)2681-2691
Number of pages11
JournalMolecular cancer therapeutics
Volume7
Issue number9
DOIs
Publication statusPublished - Oct 22 2008

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this