Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells.
Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells.
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发表时间：
2009
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通讯作者：
Hao Jiang;Xia Shang;Hongtao Wu;S. Gautam;Shaza N Al-Holou;Christina Li;J. Kuo;Lijie Zhang;M. Chopp
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作者：
Hao Jiang;Xia Shang;Hongtao Wu;S. Gautam;Shaza N Al-Holou;Christina Li;J. Kuo;Lijie Zhang;M. Chopp
白藜芦醇（反式-3，4 '，5-三羟基芪）是一种天然存在的多酚化合物，具有抗氧化、神经保护和化学预防作用。白藜芦醇导致细胞周期停滞，并诱导各种类型的癌细胞凋亡。在本研究中，白藜芦醇对磷脂酰肌醇激酶-3（PI 3 K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的影响在人胶质瘤细胞U251中被检查。白藜芦醇降低Akt的表达和磷酸化。PI 3 K（LY 294002）和Akt（SH-6）抑制剂增强白藜芦醇诱导的LDH释放和caspase-3激活。白藜芦醇减少核糖体蛋白S6的磷酸化，mTOR抑制剂雷帕霉素进一步增强白藜芦醇诱导的细胞死亡。这些结果提示PI 3 K/Akt/mTOR信号通路的下调可能是白藜芦醇诱导胶质瘤细胞凋亡的重要介质。
Resveratrol (trans-3,4', 5-trihydroxystilbene) is a naturally occurring polyphenolic compound that has antiinflammatory, antioxidant, neuroprotective properties and acts as a chemopreventive agent. Resveratrol causes cell cycle arrest and induces apoptotic cell death in various types of cancer cells. In the current studies, the effect of resveratrol on phosphoinositide kinase-3 (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Resveratrol decreased both the expression and phosphorylation of Akt. Inhibitors of PI3K (LY294002) and Akt (SH-6) enhanced resveratrol-induced LDH release and caspase-3 activation. Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death. These results suggest that the downregulation of PI3K/Akt/mTOR signaling pathways may be an important mediator in resveratrol-induced apoptosis in glioma cells.