Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Nutr Cancer. 2012;64(4):599-606. doi: 10.1080/01635581.2012.665564. Epub 2012 Apr 6.
Myricetin, a naturally occurring phytochemical, has potent anticancer-promoting activity and contributes to the chemopreventive potential of several foods. In this preliminary study, we evaluate the chemopreventive potential of myricetin against bladder cancer and its mechanism of action. The results of a MTT assay showed that myricetin was able to inhibit the viability and proliferation of T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G2/M in a dose-dependent manner and induced apoptosis detected by flow cytometry and DNA fragmentation analysis. Treatment with myricetin led to G2/M cell cycle arrest in T24 cells by downregulation of Cyclin B1 and cyclin-dependent kinase cdc2. Myricetin-induced apoptosis correlates with the modulation of Bcl-2 family proteins and activation of the caspase-3. Myricetin also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. Myricetin had a significantly reduced T24 cell migration that was accompanied by a decreasing MMP-9 expression in vitro. Furthermore, myricetin treatment significantly inhibited the tumor growth on T24 bladder cancer xenografts model. These findings suggest that myricetin has potential anticancer activity and could be an important chemoprevention agent for bladder cancer.
杨梅素是一种天然存在的植物化学物质,具有很强的抗癌促进活性,并为几种食物的化学预防潜力做出贡献。在这项初步研究中,我们评估了杨梅素对膀胱癌的化学预防潜力及其作用机制。MTT 分析结果表明,杨梅素能够以剂量和时间依赖的方式抑制 T24 细胞的活力和增殖。它还通过流式细胞术和 DNA 片段分析检测到的细胞周期阻滞在 G2/M 期呈剂量依赖性诱导细胞凋亡。杨梅素通过下调细胞周期蛋白 B1 和细胞周期蛋白依赖性激酶 cdc2 导致 T24 细胞 G2/M 细胞周期阻滞。杨梅素诱导的细胞凋亡与 Bcl-2 家族蛋白的调节和 caspase-3 的激活有关。杨梅素还抑制 Akt 的磷酸化,而 p38 MAPK 的磷酸化增强。杨梅素显著降低 T24 细胞迁移,体外 MMP-9 表达降低。此外,杨梅素处理显著抑制 T24 膀胱癌异种移植模型中的肿瘤生长。这些发现表明,杨梅素具有潜在的抗癌活性,可能是膀胱癌的重要化学预防剂。