Hsieh Tze-Chen, Xiong Wen, Traganos Frank, Darzynkiewicz Zbigniew, Wu Joseph M
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
Anticancer Res. 2002 Jul-Aug;22(4):2051-60.
Previous studies have suggested that the clinical efficacy of PC-SPES, a dietary supplement used frequently by men diagnosed with androgen-dependent (AD) or androgen-independent (AI) prostate cancer (CaP), is mechanistically attributed to estrogenic components present in the herbal mixture. To test this hypothesis, we compared estradiol (1 nM), potentially an active principle in PC-SPES, with PC-SPES (using an amount equivalent to 1 nM estradiol) on cell proliferation, induction of apoptosis, and regulation of prostate specific genes, PSA and AR, in androgen-responsive LNCaP cells. Cells cultured in steroid-proficient (FBS) or-deficient (CS-FBS) media to simulate hormonal status pre- and post-castration in vivo, were incubated with estradiol or PC-SPES. Proliferation was reduced in PC-SPES treated cells cultured in media supplemented with FBS or CS-FBS; in contrast, addition of estradiol had no effect on proliferation in FBS cultures, and elicited a 45% growth increase in CS-PBS-supplemented cultures. The differential proliferative response of LNCaP cells to PC-SPES vs. estradiol was also supported by changes in PCNA expression, cell viability, cell cycle phase distribution, and induction of apoptosis. Estradiol elicited time-dependent increases in secreted PSA, whereas PC-SPES suppressed PSA secretion, in both culture conditions. In FBS cultures, PC-SPES lowered intracellular AR and PSA by 61% and 17%, respectively, while estradiol increased intracellular PSA, in parallel with a 42% decrease in AR expression. In comparison with cells maintained with CS-FBS, estradiol induced substantial increases in both intracellular PSA and AR, whereas PC-SPES resulted in a smaller increase in intracellular PSA without affecting the expression of AR. These studies show that the antiproliferative and gene modulatory effects of PC-SPES in androgen-dependent human prostate cancer cells are mechanistically and functionally distinct from effects attributable to estradiol.
先前的研究表明，PC-SPES是一种常被诊断为雄激素依赖性（AD）或雄激素非依赖性（AI）前列腺癌（CaP）的男性频繁使用的膳食补充剂，其临床疗效在机制上归因于草药混合物中存在的雌激素成分。为了验证这一假设，我们将PC-SPES（使用相当于1 nM雌二醇的量）与雌二醇（1 nM），后者可能是PC-SPES中的一种活性成分，在雄激素反应性LNCaP细胞的细胞增殖、凋亡诱导以及前列腺特异性基因PSA和AR的调节方面进行了比较。在富含类固醇（FBS）或缺乏类固醇（CS-FBS）的培养基中培养细胞以模拟体内去势前后的激素状态，然后用雌二醇或PC-SPES进行孵育。在补充有FBS或CS-FBS的培养基中培养的经PC-SPES处理的细胞增殖减少；相反，添加雌二醇对FBS培养物中的增殖没有影响，而在补充有CS-PBS的培养物中引起45%的生长增加。PCNA表达、细胞活力、细胞周期阶段分布和凋亡诱导的变化也支持了LNCaP细胞对PC-SPES与雌二醇的不同增殖反应。在两种培养条件下，雌二醇引起分泌的PSA随时间增加，而PC-SPES抑制PSA分泌。在FBS培养物中，PC-SPES使细胞内AR和PSA分别降低61%和17%，而雌二醇增加细胞内PSA，同时AR表达降低42%。与用CS-FBS培养的细胞相比，雌二醇诱导细胞内PSA和AR都大幅增加，而PC-SPES导致细胞内PSA的增加较小，且不影响AR的表达。这些研究表明，PC-SPES在雄激素依赖性人前列腺癌细胞中的抗增殖和基因调节作用在机制和功能上与雌二醇的作用不同。
