Gapter Leslie, Wang Zaisen, Glinski Jan, Ng Ka-yun
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Biochem Biophys Res Commun. 2005 Jul 15;332(4):1153-61. doi: 10.1016/j.bbrc.2005.05.044.
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.
茯苓酸（PA）是一种天然三萜类化合物，已知其能抑制产生花生四烯酸（AA）的磷脂酶A2（PLA₂）家族的酶。PLA₂在前列腺腺癌中水平升高，AA转化为前列腺素会导致AKT的促生存活性。在本研究中，我们调查了PA对人前列腺癌细胞生长的影响。PA以剂量和时间依赖性方式显著降低细胞增殖并诱导凋亡，相对于雄激素反应性LNCaP细胞，雄激素不敏感的DU145前列腺癌细胞表现出更大的生长抑制。尽管细胞周期抑制剂p21的蛋白表达升高，但凋亡在没有细胞周期停滞的情况下发生。PA处理降低了Bad的磷酸化，增加了Bcl-2的磷酸化，并激活了caspases-9和-3，表明PA通过线粒体功能障碍引发凋亡。PA处理还降低了AKT信号通路中蛋白质的表达和激活。我们推测PA通过减少前列腺素合成和AKT活性影响凋亡。
