Hsieh T C, Wu J M
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
Exp Cell Res. 1999 May 25;249(1):109-15. doi: 10.1006/excr.1999.4471.
Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2. 5 x 10(-5)-10(-7) M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 x 10(-5) M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.
流行病学研究表明，营养在致癌过程中起着重要作用，通过适当调整饮食，30%的癌症发病率和死亡率有可能得到预防。白藜芦醇是一种存在于红酒和多种人类食物中的多酚，最近有报道称，在小鼠皮肤癌模型系统中进行测试时，它具有化学预防特性。在本研究中，我们使用模拟前列腺癌初始（激素敏感）和晚期（激素抵抗）阶段的培养前列腺癌细胞，研究了白藜芦醇对细胞生长、凋亡诱导以及前列腺特异性基因表达调节的影响。将雄激素反应性LNCaP和雄激素无反应性DU - 145、PC - 3及JCA - 1人前列腺癌细胞与不同浓度的白藜芦醇（2.5×10⁻⁵ - 10⁻⁷ M）一起培养。测定细胞生长、细胞周期分布和凋亡情况。添加2.5×10⁻⁵ M白藜芦醇导致LNCaP以及PC - 3和DU - 145细胞的生长显著下降，但对JCA - 1细胞的增殖只有适度的抑制作用。流式细胞术分析表明，白藜芦醇在所有三种雄激素无反应性细胞系中部分破坏G1/S转换，但对雄激素反应性LNCaP细胞没有影响。然而，与雄激素无反应性前列腺癌细胞不同，白藜芦醇使相当比例的LNCaP细胞发生凋亡，并显著降低细胞内和分泌的前列腺特异性抗原（PSA）水平，而不影响雄激素受体（AR）的表达。这些结果表明，白藜芦醇以前列腺细胞类型特异性方式通过影响有丝分裂以及诱导凋亡来负向调节前列腺癌细胞生长。白藜芦醇还通过一种不依赖AR的机制调节PSA基因表达。
