Cytotoxic effect of bitter melon (Momordica charantia L.) ethanol extract and its fractions on pancreatic cancer cells in vitro

Background and objectives: The incidence of pancreatic cancer (PC) closely matches mortality, with current therapies ineffective often due to late diagnosis and difficulties in drug delivery. Bitter melon (Momordica charantia, Cucurbitaceae) has been traditionally used as an herbal medicine, particularly for the treatment of diabetes, in South East Asian countries. The aim of this study was to investigate the anti-PC potential of a crude ethanol extract (CE) and its enriched fractions. Methods: The CE was used to prepare the saponin-enriched extract (SE) using n-butanol: water extraction. CE was also used for preparation of fractions 1, 2 and 3 (F1, F2 & F3) with a semi-preparative high-pressure liquid chromatography system. Cucurbitacin B (CuB), a triterpenoid present in many Cucurbitaceae species was also investigated for its effect on PC cells. The cytotoxicity was assessed in the PC cells MiaPaCa2, BxPC3 and CFPAC-1, and normal pancreas cells (HPDE) using the Cell Counting Kit-8 viability assay. Cell cycle analysis and induction of apoptosis in cells treated with F3 or CuB was determined using the Muse™ flow cell analyzer. Results: The CE reduced the viability of MiaPaCa2 cells without affecting the normal cells, but only at 1,000 µg/mL. The SE reduced viability of all cells; however, the GI50 was significantly lower for the HPDE cells (72h: 72.1 µg/mL HPDE vs. 350.8 µg/mL MiaPaCa2). F3 and CuB appeared to arrest the cell cycle at G1/0 and G2/M, respec-tively; however, only CuB induced apoptosis via increased expression of caspase 3/7. Conclusions: The CE, SE and three fractions elicited a weak cytotoxic effect on PC cells. Further research into bitter melon is recommended to isolate and identify any active components in F3 and further investigate their potential as novel agents against PC.