Abstract
Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW) and skin (BMSk) extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.
Highlights
Colorectal cancer is the second leading cause of cancer related deaths and the third most commonly occurring noncutaneous carcinoma in the United States of America [1]
We present the results of our in vitro experiments showing that methanolic extracts of bitter melon (BMW) inhibit cell proliferation, prevent colony formation, and promote S phase cell cycle arrest of colon cancer cells
To determine whether bitter melon extracts affect cell proliferation, the cells were grown in the presence of varying concentrations of bitter melon whole fruit extracts (BMW) and BMSk (0– 500 μg/mL) for 48 h and the cell proliferation was measured by hexoseminidase assay
Summary
Colorectal cancer is the second leading cause of cancer related deaths and the third most commonly occurring noncutaneous carcinoma in the United States of America [1]. Early diagnosis often leads to a complete cure, in most cases the polyps go undetected. In such cases, therapies such as surgical intervention, chemotherapy, and radiation are often not sufficient to tackle the disease, needing other prevention-related or nonconventional therapeutic strategies. Studies have shown that bitter melon extracts are well tolerated in both acute and chronic doses in animals [9,10,11]. Recent studies have demonstrated that aqueous extracts of bitter melon can inhibit the growth of Evidence-Based Complementary and Alternative Medicine breast and prostate cancers [12,13,14]. Though the mechanisms behind the antitumor activity are poorly known, the previous studies hint towards induction of apoptosis as one potential mechanism [15, 16]
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