Sgambato A, Ardito R, Faraglia B, Boninsegna A, Wolf F I, Cittadini A
Centro di Ricerche Oncologiche "Giovanni XXIII", Istituto di Patologia Generale, Catholic University, Largo Francesco Vito 1, 00168, Rome, Italy.
Mutat Res. 2001 Sep 20;496(1-2):171-80. doi: 10.1016/s1383-5718(01)00232-7.
Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phenolic compound which is present at high levels in wine and has been recently proposed as a potential cancer chemopreventive and chemoterapeutic agent. In this study, we evaluated the antiproliferative activity of resveratrol on a panel of cell lines of various histogenetic origin, including normal rat fibroblasts and mouse mammary epithelial cells compared to human breast, colon and prostate cancer cells. The concentration of resveratrol inhibiting cell growth by 50% (IC(50)) ranged from about 20 to 100 microM. At such concentration, we were unable to detect a significant increase in the apoptotic index in most of the cell lines analyzed. We also studied the effects of resveratrol on cell cycle distribution. The most striking effect was a reduction in the percentage of cells in the G2/M phase which was most frequently associated with an increase of cells in the S phase of the cell cycle. We also found that resveratrol is able to prevent the increase in reactive oxygen species (ROS) following exposure to oxidative agents (i.e. tobacco-smoke condensate (TAR) and H(2)O(2)). Resveratrol also reduced nuclear DNA fragmentation, as assessed by single cell gel electrophoresis (comet test). Taken together our results suggest that resveratrol can act as an antimutagenic/anticarcinogenic agent by preventing oxidative DNA damage which plays a pivotal role in the carcinogenic activity of many genotoxic agents.
白藜芦醇(3,4',5-三羟基茋)是一种天然存在的酚类化合物,在葡萄酒中含量很高,最近被提议作为一种潜在的癌症化学预防和化学治疗剂。在本研究中,我们评估了白藜芦醇对一系列不同组织发生来源的细胞系的抗增殖活性,包括正常大鼠成纤维细胞和小鼠乳腺上皮细胞,并与人类乳腺癌、结肠癌和前列腺癌细胞进行比较。白藜芦醇抑制细胞生长50%(IC50)的浓度范围约为20至100微摩尔。在这样的浓度下,我们在大多数分析的细胞系中未能检测到凋亡指数的显著增加。我们还研究了白藜芦醇对细胞周期分布的影响。最显著的影响是G2/M期细胞百分比的降低,这最常与细胞周期S期细胞的增加相关。我们还发现白藜芦醇能够防止暴露于氧化剂(即烟草烟雾浓缩物(TAR)和H2O2)后活性氧(ROS)的增加。通过单细胞凝胶电泳(彗星试验)评估,白藜芦醇还减少了核DNA片段化。综合我们的结果表明,白藜芦醇可以通过防止氧化DNA损伤来充当抗诱变/抗癌剂,氧化DNA损伤在许多遗传毒性剂的致癌活性中起关键作用。