Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo
Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo
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DOI：
10.1111/j.1349-7006.2009.01415.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Xie, Li-Ping
中科院分区：
文献类型：
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作者：
Bai, Yu;Mao, Qi-Qi;Xie, Li-Ping
白藜芦醇是葡萄和红酒中天然存在的多酚类抗氧化化合物，据报道具有多种生化反应。在本初步研究中，我们评价了白藜芦醇对膀胱癌的化学预防潜力及其作用机制。用白藜芦醇治疗膀胱癌细胞导致细胞活力显著降低。白藜芦醇通过调节Bcl-2家族蛋白，激活caspase 9和caspase 3，随后进行聚（adp -核糖）聚合酶降解，诱导细胞凋亡。白藜芦醇通过激活p21，下调cyclin D1、cyclin依赖性激酶4和磷酸化Rb，导致T24细胞G1期细胞周期阻滞。白藜芦醇还能抑制Akt的磷酸化，而p38 MAPK的磷酸化则增强。此外，白藜芦醇处理降低了血管内皮生长因子和成纤维细胞生长因子-2的表达，这可能与抑制膀胱癌异种移植模型的肿瘤生长有关。这些发现表明，白藜芦醇可能是一种重要的膀胱癌化学预防剂。（癌症科学2010；101:488-493）
Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP-ribose) polymerase degradation. Treatment with resveratrol led to G1 phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin-dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor-2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer. (Cancer Sci 2010; 101: 488-493)