Bitter Melon Juice Induces Apoptotic Death Of Human Pancreatic Carcinoma Cells

Pancreatic cancer is one of the deadliest cancers. The prognosis of this malignancy is extremely poor in general and especially at advanced stages of the disease, suggesting that newer preventive/intervention strategies are necessary to improve the outcome of this malignancy. Plant based therapies are often used as alternative and complementary treatments for various diseases including cancer. Bitter melon (Momordica Charantia) is a fruit from the perennially growing climber of Cucurbitacae family. It is a commonly consumed vegetable and is also used as a traditional medicine for treating disease conditions such as diabetes, ulcers, microbial and viral infections, etc. In recent years, the interest in its anti-cancer potential has grown considerably in the scientific community; however, literature still lacks detailed studies on this aspect. In the present study, we assessed the efficacy and associated mechanisms of bitter melon juice (BMJ) against pancreatic cancer. For this, we selected two human pancreatic cancer cell lines, BxPC-3 and MiaPaCa-2, which differ in K-ras status; a major genetic alteration in most pancreatic cancer cases. We observed that treatment of these cells with BMJ (2-4% v/v) significantly decreases the viability by 59-94% and 40-91% after 48h in case of BxPC-3 and MiaPaCa-2 cells, respectively. Decrease in cell viability was largely due to apoptosis induction as evidenced by cell death ELISA and western blot analysis for cleaved caspases-9 and -3. A significant increase in the release of cytochrome-c in the cytoplasmic fraction was also observed, thereby indicating that BMJ activates the intrinsic pathway of apoptosis in these cell lines. Additionally, BMJ significantly increased the levels of pro-apoptotic protein Bak and decreased the levels of anti-apoptotic protein Bcl-XL in both the cell lines. In other studies, BMJ treatment down-regulated XIAP and survivin, but increased p21 and Chop, and caused an activation of ERK and p38 in both cell lines without any effect on JNK. Furthermore, BMJ treatment resulted in significant up regulation in AMPK activation thereby suggesting it might be impinging on additional pathways. In tumor xenograft study, administration of lyophilized BMJ powder in diet (1.5%, w/w) to athymic nude mice for 42 days caused a significant inhibition in MiaPaca-2 xenograft growth in terms of a decrease in tumor volume by 43% (P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1612. doi:1538-7445.AM2012-1612