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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 702869, 14 pages
http://dx.doi.org/10.1155/2013/702869
Research Article

Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

1Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard MS 3040, Kansas City, KS 66160, USA
2University of Kansas Cancer Center, University of Kansas Medical Center, 3901 Rainbow Boulevard MS 3040, Kansas City, KS 66160, USA
3Department of Pharmacognosy, Vels University, Pallavaram, Chennai 600117, India
4Department of Pharmaceutical Sciences, University of Missouri at Kansas City, Kansas City, MO 64108, USA

Received 18 September 2012; Revised 21 January 2013; Accepted 29 January 2013

Academic Editor: Mani Vasudevan

Copyright © 2013 Deep Kwatra 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.

Abstract

Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW) and skin (BMSk) extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.