Cyproheptadine exhibits antitumor activity in urothelial carcinoma cells by targeting GSK3β to suppress mTOR and β-catenin signaling pathways

Hsiao Yen Hsieh, Cheng Huang Shen, Ru Inn Lin, Yu Min Feng, Shih Yuan Huang, Yuan Hung Wang, Shu Fen Wu, Cheng Da Hsu, Michael W.Y. Chan

研究成果: 雜誌貢獻文章同行評審

23 引文 斯高帕斯(Scopus)

摘要

Cyproheptadine, a serotonin antagonist, has recently been reported to function as a novel therapeutic agent by inhibiting PI3K/AKT signaling in several human cancers. However, the therapeutic effect of cyproheptadine in urothelial carcinoma (UC) has never been explored. In this study, we determined the effect of cyproheptadine on the growth of five human UC cell lines and an in vivo xenograft model. The results showed that cyproheptadine exerted an inhibitory effect on the proliferation of UC cells both in vitro and in vivo. Cyproheptadine also induced cell cycle arrest in the G1 phase, subsequently followed by apoptosis and necrosis. The underlying mechanisms of cell cycle arrest were associated with the reduction of c-Myc, induction of p21 and p27, and the stabilization of Rb expression. In addition, the suppression of the GSK3β/TSC2/mTOR pathway and deregulation of the GSK3β/β-catenin signaling were observed in cyproheptadine-treated UC cells. Furthermore, cyproheptadine-induced apoptosis was associated with ANGPTL4 expression followed by activation of caspase3 and PARP in UC cells. Our experimental results provide evidence that cyproheptadine is a suitable therapeutic agent for the treatment of UC.

原文英語
頁(從 - 到)56-65
頁數10
期刊Cancer Letters
370
發行號1
DOIs
出版狀態已發佈 - 1月 1 2016

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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