Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/26/2016
Publication Date: 9/15/2016
Publication URL: http://handle.nal.usda.gov/10113/63140
Citation: Dia, V.P., Krishnan, H.B. 2016. BG-4, a novel anticancer peptide from bitter gourd (Momordica charantia), promotes apoptosis in human colon cancer cells. Scientific Reports. doi:10.1038/srep33532.

Interpretive Summary: Consumption of soy/soy products has been shown to reduce the risk for breast, colon and prostate cancer. Soy protease inhibitors have also been documented to beve anti-cancer agents. Recently, we have devised a rapid, simple and an inexpensive method to isolate large quantities of protease inhibitors from soybean. During the course of that investigation we also observed that seeds of bitter gourd, a perennial plant with reported health benefits, accumulate large amounts of protease inhibitors. By modification the procedure that we developed for the isolation of soybean protease inhibitor, we were able to obtain large quantities of biologically active protease inhibitor from bitter gourd seeds. The purified protease inhibitor was found to very effective against human colon cancer cells. Information from this study will enable scientists to exploit protease inhibitors from plant sources such as soybean and bitter gourd for potential therapeutic use against colon cancer.

Technical Abstract: Momordica charantia is a perennial plant with reported health benefits. BG-4, a novel peptide from Momordica charantia, was isolated, purified and characterized. The trypsin inhibitory activity of BG-4 is 8.6 times higher than purified soybean trypsin inhibitor. The high trypsin inhibitory activity of BG-4 may be responsible for its capability to cause cytotoxicity to HCT-116 and HT-29 human colon cancer cells with ED50 values of 134.4 and 217.0 µg/mL after 48 h of treatment, respectively. The mechanism involved in the cytotoxic effect may be associated with induction of apoptosis as evidenced by increased percentage of HCT-116 and HT-29 colon cancer cells undergoing apoptosis from 5.4% (untreated) to 24.8% (BG-4 treated, 125 µg/mL for 16 h) and 8.5% (untreated) to 31.9% (BG-4 treated, 125 µg/mL for 16 h), respectively. In HCT-117 colon cancer cells, the molecular mechanistic explanation in the apoptosis inducing property of 125 µg/mL is due to reduced expression of Bcl-2 and increased expression of Bax leading to decreased expression of XIAP and increased expression of caspase-3. This is the first report on the anti-cancer potential of a novel bioactive peptide isolated from Momordica charantia supporting the potential therapeutic property of BG-4 against colon cancer.