Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling Cascade.
Objective Acquired chemoresistance is a major obstacle in the clinical management of ovarian cancer. Therefore, searching for alternative therapeutic modalities is urgently needed. Bitter melon (Momordica charantia) is a traditional dietary fruit, but its extract also shows potential medicinal values in human diabetes and cancers. Here, we sought to investigate the extract of bitter melon (BME) in antitumorigenic and cisplatin-induced cytotoxicity in ovarian cancer cells.



Three varieties of bitter melon were used to prepare the BME. Ovarian cancer cell lines, human immortalized epithelial ovarian cells (HOSEs), and nude mice were used to evaluate the cell cytotoxicity, cisplatin resistance, and tumor inhibitory effect of BME. The molecular mechanism of BME was examined by Western blotting.



Cotreatment with BME and cisplatin markedly attenuated tumor growth in vitro and in vivo in a mouse xenograft model, whereas there was no observable toxicity in HOSEs or in nude mice in vivo Interestingly, the antitumorigenic effects of BME varied with different varieties of bitter melon, suggesting that the amount of antitumorigenic substances may vary. Studies of the molecular mechanism demonstrated that BME activates AMP-activated protein kinase (AMPK) in an AMP-independent but CaMKK (Ca(2+)/calmodulin-dependent protein kinase)-dependent manner, exerting anticancer effects through activation of AMPK and suppression of the mTOR/p70S6K and/or the AKT/ERK/FOXM1 (Forkhead Box M1) signaling cascade.



BME functions as a natural AMPK activator in the inhibition of ovarian cancer cell growth and might be useful as a supplement to improve the efficacy of cisplatin-based chemotherapy in ovarian cancer.
The University of Hong Kong, Hong Kong SAR, P R China.
Mingo M H
MM
Yung
University of Dundee, Dundee, Scotland, UK.
Fiona A
FA
Ross
University of Dundee, Dundee, Scotland, UK.
D Grahame
DG
Hardie
The University of Hong Kong, Hong Kong SAR, P R China.
Thomas H Y
TH
Leung
Zhejiang University, Hangzhou, P R China.
Jinbiao
J
Zhan
The University of Hong Kong, Hong Kong SAR, P R China.
Hextan Y S
HY
Ngan
The University of Hong Kong, Hong Kong SAR, P R China dwchan@hku.hk.
David W
DW
Chan
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D029777:Momordica charantia / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases; D002945:Cisplatin
AMPK activator; Momordica charantia; bitter melon; chemoresistance; cisplatin; ovarian cancer