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Biochem Biophys Res Commun. 2005 Jul 15;332(4):1153-61.

Induction of apoptosis in prostate cancer cells by pachymic acid from Poria cocos.

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1
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

Erratum in

  • Biochem Biophys Res Commun. 2006 Jan 6;339(1):457.

Abstract

Pachymic acid (PA) is a natural triterpenoid known to inhibit the phospholipase A2 (PLA(2)) family of arachidonic acid (AA)-producing enzymes. PLA(2) is elevated in prostatic adenocarcinoma and conversion of AA to prostaglandins leads to AKT pro-survival activity. In this study, we investigated the effect of PA on the growth of human prostate cancer cells. PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway. We speculate that PA influenced apoptosis by reducing prostaglandin synthesis and AKT activity.

PMID:
15913545
DOI:
10.1016/j.bbrc.2005.05.044
[Indexed for MEDLINE]

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