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Resveratrol Induces Glioma Cell Apoptosis through Activation of Tristetraprolin
Authors:Jinhyun Ryu  Nal Ae Yoon  Hyemin Seong  Joo Yeon Jeong  Seokmin Kang  Nammi Park  Jungil Choi  Dong Hoon Lee  Gu Seob Roh  Hyun Joon Kim  Gyeong Jae Cho  Wan Sung Choi  Jae-Yong Park  Jeong Woo Park  Sang Soo Kang
Abstract:Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of AREs-containing mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4′-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3′ untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.
Keywords:apoptosis   glioma   resveratrol   TTP   uPA   uPAR
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