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2016 ; 15
(3
): 376-89
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Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes
Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling
Cascade
#MMPMID26487740
Yung MM
; Ross FA
; Hardie DG
; Leung TH
; Zhan J
; Ngan HY
; Chan DW
Integr Cancer Ther
2016[Sep]; 15
(3
): 376-89
PMID26487740
show ga
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.
METHODS: 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. RESULTS: 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. CONCLUSION: 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.