Sun Xiuli, Zhang Yi, Wang Jianliu, Wei Lihui, Li Hui, Hanley Gregory, Zhao Miaoqing, Li Yi, Yin Deling
Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China.
Biochim Biophys Acta. 2010 Sep;1800(9):912-8. doi: 10.1016/j.bbagen.2010.04.015. Epub 2010 May 7.
Resveratrol is emerging as a novel anticancer agent. However, the mechanism(s) by which resveratrol exerts its effects on endometrial cancer (EC) are unknown. We previously reported that beta-arrestin 2 plays a critical role in cell apoptosis. The role of ß-arrestin 2 in resveratrol modulation of endometrial cancer cell apoptosis remains to be established.
EC cells HEC1B and Ishikawa were transfected with either ß-arrestin 2 RNA interfering (RNAi) plasmid or beta-arrestin 2 full-length plasmid and control vector. The cells were then exposed to differing concentrations of resveratrol. Apoptotic cells were detected by TUNEL assay. Expression of total and phosphorylated Akt (p-Akt), total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3ß), and caspase-3 were determined by Western blot analysis. Our data demonstrate that inhibition of ß-arrestin 2 increases the number of apoptotic cells and caspase-3 activation. Additionally ß-arrestin 2 exerted an additive effect on resveratrol-reduced levels of p-Akt and p-GSK3ß. Overexpression of ß-arrestin 2 decreased the percentage of apoptosis and caspase-3 activation and attenuated resveratrol-reduced levels of p-Akt and p-GSK3ß. Taken together, our studies demonstrate for the first time that ß-arrestin 2 mediated signaling plays a critical role in resveratrol-induced apoptosis in EC cells.
Resveratrol primes EC cells to undergo apoptosis by modulating beta-arrestin 2 mediated Akt/GSK3ß signaling pathways.
These inspiring findings would provide a new molecular basis for further understanding of cell apoptotic mechanisms mediated by ß-arrestin 2 and may provide insights into a potential clinical relevance in EC.
白藜芦醇正成为一种新型抗癌剂。然而，白藜芦醇对子宫内膜癌（EC）发挥作用的机制尚不清楚。我们之前报道过β - 抑制蛋白2在细胞凋亡中起关键作用。β - 抑制蛋白2在白藜芦醇调节子宫内膜癌细胞凋亡中的作用仍有待确定。
将EC细胞HEC1B和Ishikawa用β - 抑制蛋白2 RNA干扰（RNAi）质粒或β - 抑制蛋白2全长质粒及对照载体进行转染。然后将细胞暴露于不同浓度的白藜芦醇中。通过TUNEL法检测凋亡细胞。通过蛋白质印迹分析确定总Akt（p - Akt）、磷酸化Akt、总糖原合酶激酶3β（p - GSK3β）、磷酸化糖原合酶激酶3β以及半胱天冬酶 - 3的表达。我们的数据表明，抑制β - 抑制蛋白2会增加凋亡细胞数量和半胱天冬酶 - 3的激活。此外，β - 抑制蛋白2对白藜芦醇降低的p - Akt和p - GSK3β水平具有累加效应。β -抑制蛋白2的过表达降低了凋亡百分比和半胱天冬酶 - 3的激活，并减弱了白藜芦醇降低的p - Akt和p - GSK3β水平。综上所述，我们的研究首次证明β - 抑制蛋白2介导的信号传导在白藜芦醇诱导的EC细胞凋亡中起关键作用。
白藜芦醇通过调节β - 抑制蛋白2介导的Akt/GSK3β信号通路促使EC细胞发生凋亡。
这些鼓舞人心的发现将为进一步理解β - 抑制蛋白2介导的细胞凋亡机制提供新的分子基础，并可能为EC的潜在临床相关性提供见解。
