Bitter melon juice activates cellular energy sensor AMPactivated protein kinase causing apoptotic death of human pancreatic carcinoma cells
Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. Here, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by MTT, cell death ELISA and annexin/PI assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2-5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl2 family members, and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and XIAP but increased p21, CHOP and phosphorylated MAPKs (ERK1/2 and p38) levels. Importantly, BMJ activated AMPactivated protein kinase (AMPK); a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase 3 activation suggesting activated-AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5 mg in 100 µl water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (p<0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anti-cancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness
Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Ray RB, Raychoudhuri A, Steele R, Nerurkar P.
Department of Pathology, Saint Louis University, St. Louis, Missouri 63104, USA.
Abstract Breast cancer is one of the most common cancers among women in the United States. Although there are effective drugs for treating advanced stages of breast cancers, women eventually develop resistance. One of the approaches to control breast cancer is prevention through diet, which inhibits one or more neoplastic events and reduces cancer risk. In this study, we have used human breast cancer cells, MCF-7 and MDA-MB-231, and primary human mammary epithelial cells as an in vitro model to assess the efficacy of bitter melon (Momordica charantia) extract (BME) as an anticancer agent. BME treatment of breast cancer cells resulted in a significant decrease in cell proliferation and induced apoptotic cell death. Apoptosis of breast cancer cells was accompanied by increased poly(ADP-ribose) polymerase cleavage and caspase activation. Subsequent studies showed that BME treatment of breast cancer cells inhibited survivin and claspin expression. Fluorescence-activated cell sorting analysis suggested that MCF-7 cells treated with BME accumulated during the G2-M phase of the cell cycle. Further studies revealed that BME treatment enhanced p53, p21, and pChk1/2 and inhibited cyclin B1 and cyclin D1 expression, suggesting an additional mechanism involving cell cycle regulation. Together, these results show that BME modulates signal transduction pathways for inhibition of breast cancer cell growth and can be used as a dietary supplement for prevention of breast cancer.