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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2050-2060
Number of pages11
JournalCarcinogenesis
Volume34
Issue number9
DOIs
Publication statusPublished - Sep 2013

ASJC Scopus subject areas

  • Cancer Research

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    Lai, C. Y., Pan, S. L., Yang, X. M., Chang, L. H., Chang, Y. L., Yang, P. C., Lee, K. H., & Teng, C. M. (2013). Depletion of 4E-BP1 and regulation of autophagy lead to YXM110-induced anticancer effects. Carcinogenesis, 34(9), 2050-2060. https://doi.org/10.1093/carcin/bgt146