pachymic-acid and Prostatic-Neoplasms

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.

Topics: Antineoplastic Agents; Apoptosis; bcl-Associated Death Protein; Carrier Proteins; Caspase 3; Caspase 9; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Coloring Agents; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Epithelial Cells; Flow Cytometry; Humans; Male; Mitochondria; Models, Chemical; Phosphorylation; Polyporales; Prostaglandins; Prostatic Neoplasms; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction; Terpenes; Time Factors; Triterpenes