Gao Xiaohua, Liu Yongbo, Deeb Dorrah, Arbab Ali S, Gautam Subhash C
J Exp Ther Oncol. 2014;10(4):275-83.
Pristimerin isaquinonemethidetriterpenoidthathasshown anticancer activity against some cancer types. However, the antitumor effects of pristimerin (PM) in ovarian cancer cells have not been adequately studied. The objective of the present study was to determine the anticancer activity and its mechanism of action in human ovarian carcinoma cell lines. PM strongly inhibited the proliferation of ovarian cancer cells by inducing apoptosis characterized by increased annexin V-binding, cleavage of poly (ADP-ribose) polymerase (PARP-1) and procaspases-3, -8 and -9. Furthermore, PM caused mitochondrial depolarization. Western blot analysis showed inhibition of prosurvival phospho-AKT (p-AKT), nuclear factor kappa B (NF-κB) (p65) and phospho-mammalian target of rapamycin (p-mTOR) signaling proteins in cells treated with PM. Treatment with PM also inhibited the expression of NF-κB-regulated antiapoptotic Bcl-2, Bcl-xL, c-IAP1 and survivin. Thus, our data showing potent antiproliferative and apoptosis-inducing activity of PM in ovarian carcinoma cells through the inhibition of AKT/ NF-κB/ mTOR signaling pathway warrant further investigation of PM for the management of ovarian cancer.
土槿皮甲酸是一种醌甲基三萜类化合物，已显示出对某些癌症类型具有抗癌活性。然而，土槿皮甲酸（PM）对卵巢癌细胞的抗肿瘤作用尚未得到充分研究。本研究的目的是确定其在人卵巢癌细胞系中的抗癌活性及其作用机制。PM通过诱导凋亡强烈抑制卵巢癌细胞的增殖，其特征为膜联蛋白V结合增加、聚（ADP-核糖）聚合酶（PARP-1）以及前半胱天冬酶-3、-8和-9的裂解。此外，PM导致线粒体去极化。蛋白质印迹分析显示，在用PM处理的细胞中，存活相关的磷酸化AKT（p-AKT）、核因子κB（NF-κB）（p65）和磷酸化雷帕霉素哺乳动物靶蛋白（p-mTOR）信号蛋白受到抑制。用PM处理还抑制了NF-κB调节的抗凋亡蛋白Bcl-2、Bcl-xL、c-IAP1和生存素的表达。因此，我们的数据表明PM通过抑制AKT/NF-κB/mTOR信号通路在卵巢癌细胞中具有强大的抗增殖和诱导凋亡活性，这为进一步研究PM用于卵巢癌的治疗提供了依据。
