Potential Anticancer Activity of Myricetin in Human T24 Bladder Cancer Cells Both In Vitro and In Vivo
Potential Anticancer Activity of Myricetin in Human T24 Bladder Cancer Cells Both In Vitro and In Vivo
复制标题
杨梅素在体外和体内对人 T24 膀胱癌细胞的潜在抗癌活性
DOI：
10.1080/01635581.2012.665564
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发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Chen, Weilin
中科院分区：
文献类型：
--
作者：
Sun, Fang;Zheng, Xiang Yi;Chen, Weilin
杨梅素是一种自然产生的植物化学物质，具有强大的抗癌促进活性，有助于几种食物的化学预防潜力。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。四甲基偶氮唑盐比色法结果显示，杨梅素对T24细胞的生长和活力有抑制作用，且呈剂量和时间依赖性。通过流式细胞仪和DNA片段化分析发现，它还以剂量依赖的方式促进细胞周期于G2/M期，并诱导细胞凋亡。杨梅素通过下调Cyclin B1和Cyclin依赖的激酶cdc2的表达，导致T24细胞的G2/M期细胞周期停滞。杨梅素诱导的细胞凋亡与Bcl2家族蛋白的调控和caspase 3的激活有关。杨梅素对Akt的磷酸化也有抑制作用，对p38MAPK的磷酸化有促进作用。杨梅素在体外显著降低了T24细胞的迁移，并伴随着基质金属蛋白酶-9表达的降低。此外，杨梅素治疗可显著抑制T24膀胱癌移植瘤模型的生长。这些发现表明杨梅素具有潜在的抗癌活性，可能是一种重要的膀胱癌化学预防药物。
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.