Depletion of 4E-BP1 and regulation of autophagy lead to YXM110-induced anticancer effects

Chin Yu Lai, Shiow Lin Pan, Xiao Ming Yang, Li Hsun Chang, Ya Ling Chang, Pan Chyr Yang, Kuo Hsiung Lee, Che Ming Teng

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7 引文 斯高帕斯(Scopus)

摘要

Natural products have always been a profuse database for developing new chemotherapeutics. YXM110 is a newly synthesized phenanthroquinolizidines that exhibits excellent anticancer activity in numerous cancer cells. In this study, we examined the anticancer mechanisms of YXM110 both in vitro and in vivo. Protein level of 4E-binding protein 1, which is crucial in cap-independent translation, was decreased significantly after YXM110treatment via c-Jun N-terminal kinases-mediated proteasomal degradation. Moreover, the effects of YXM110 were associated with several characteristics of autophagy, including accumulation of autophagic vacuoles, elevation of Atg12-Atg5 and light chain 3 (LC3)-II, and levels of GFP-LC3 puncta. The results suggested that depletion of Mcl-1 contributes to YXM110-triggered autophagy, whereas downregulation of lysosomal-related genes could cause autophagy impairment. Furthermore, YXM110-induced cell death was prevented by autophagy inhibitor 3-methyladenine and Atg5 silencing, indicating that YXM110-mediatedautophagy impairment leads to cancer cell death. These data reveal key mechanisms that support the further development of YXM110 as a promising anticancer agent.
原文英語
頁(從 - 到)2050-2060
頁數11
期刊Carcinogenesis
34
發行號9
DOIs
出版狀態已發佈 - 九月 2013

ASJC Scopus subject areas

  • 癌症研究

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