Cucurbitane triterpenoid from momordica charantia induces apoptosis and autophagy in breast cancer cells, in part, through peroxisome proliferator-activated receptor γ activation

Jing Ru Weng, Li Yuan Bai, Chang Fang Chiu, Jing Lan Hu, Shih Jiuan Chiu, Chia Yung Wu

研究成果: 雜誌貢獻文章

35 引文 斯高帕斯(Scopus)

摘要

Although the antitumor activity of the crude extract of wild bitter gourd (Momordica charantia L.) has been reported, its bioactive constituents and the underlying mechanism remain undefined. Here, we report that 3β,7β- dihydroxy-25-methoxycucurbita-5,23-diene-19-al (DMC), a cucurbitane-type triterpene isolated from wild bitter gourd, induced apoptotic death in breast cancer cells through peroxisome proliferator-activated receptor (PPAR) γ activation. Luciferase reporter assays indicated the ability of DMC to activate PPARγ, and pharmacological inhibition of PPARγ protected cells from DMC's antiproliferative effect. Western blot analysis indicated that DMC suppressed the expression of many PPARγ-targeted signaling effectors, including cyclin D1, CDK6, Bcl-2, XIAP, cyclooxygenase-2, NF-B, and estrogen receptor α, and induced endoplasmic reticulum stress, as manifested by the induction of GADD153 and GRP78 expression. Moreover, DMC inhibited mTOR-p70S6K signaling through Akt downregulation and AMPK activation. The ability of DMC to activate AMPK in liver kinase (LK) B1-deficient MDA-MB-231 cells suggests that this activation was independent of LKB1-regulated cellular metabolic status. However, DMC induced a cytoprotective autophagy presumably through mTOR inhibition, which could be overcome by the cotreatment with the autophagy inhibitor chloroquine. Together, the ability of DMC to modulate multiple PPARγ-targeted signaling pathways provides a mechanistic basis to account for the antitumor activity of wild bitter gourd.

原文英語
文章編號935675
期刊Evidence-based Complementary and Alternative Medicine
2013
DOIs
出版狀態已發佈 - 2013

ASJC Scopus subject areas

  • Complementary and alternative medicine

指紋 深入研究「Cucurbitane triterpenoid from momordica charantia induces apoptosis and autophagy in breast cancer cells, in part, through peroxisome proliferator-activated receptor γ activation」主題。共同形成了獨特的指紋。

  • 引用此