Bitter melon (Momordica charantia) extract inhibits tumorigenicity and overcomes cisplatin-resistance in ovarian cancer cells through targeting AMPK signaling cascade

Abstract

Objective: Acquired chemoresistance is a major obstacle in 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 uses in human diabetes and cancers. Here, we sought to investigate the extract of bitter melon (BME) in anti-tumorigenic and cisplatin-induced cytotoxicity in ovarian cancer cells. Methods: Three varieties of bitter melon were used to prepare the bitter melon extract (BME). Ovarian cancer cell lines, human immortalized epithelial ovarian cells (HOSEs) and nude mice were used to evaluate the cell cytotoxicity, cisplatin-resistance and the tumor inhibitory effect of BME. The molecular mechanism of BME was examined by western blotting. Results: Co-treatment with BME and cisplatin markedly attenuated tumor growth in vitro and in vivo in a mouse xenograft model, while there was no observable toxicity in human immortalized epithelial ovarian cells (HOSEs) or in nude mice in vivo. Interestingly, the anti-tumorigenic effects of BME varied with different varieties of bitter melon, suggesting that the amount of anti-tumorigenic substances may vary. Studies of the molecular mechanism demonstrated that BME activates AMPK in an AMP-independent, but CaMKK-dependent manner, exerting anti-cancer effects through activation of AMPK and suppression of the mTOR/p70S6K and/or the AKT/ERK/FOXM1 signaling cascade. Conclusion: BME functions as a natural AMPK activator in inhibition of ovarian cancer cell growth, and might be useful as a supplement to improve the efficacy of cisplatin-based chemotherapy in ovarian cancer.