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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 935675, 12 pages
Research Article

Cucurbitane Triterpenoid from Momordica charantia Induces Apoptosis and Autophagy in Breast Cancer Cells, in Part, through Peroxisome Proliferator-Activated Receptor γ Activation

1Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan
2Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan
3College of Medicine, China Medical University, Taichung 40402, Taiwan
4Cancer Center, China Medical University Hospital, Taichung 40402, Taiwan
5School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan

Received 20 February 2013; Revised 24 May 2013; Accepted 26 May 2013

Academic Editor: Yoshiharu Motoo

Copyright © 2013 Jing-Ru Weng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-κB, 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.