Momordica charantia L. Induces Non-Apoptotic Cell Death in Human MDA-MB-436 Breast and A549 Lung Cancer Cells by Disrupting Energy Metabolism and Exacerbating Reactive Oxygen Species’ Generation

Abstract Ethnopharmacological relevance Bitter melon, Momordica charantia L. (MC), is an ethnomedicinal plant cultivated in different climes. It’s cytotoxic effect on several cancer cell lines has been evaluated. However, there have been contrasting reports on the actual mechanism (s) involved in the observed cell death induced by MC. Aims of the study To probe the mechanism of cell death induction in MDA-MB-436 (Breast) and A549 (lung) cancer cell lines treated with fractions (ethyl acetate, dichloromethane and hexane) derived from the aqueous extract of MC. Materials and Methods Aqeous extract of the leaves of MC were fractionated using solvents of different polarities (ethyl acetate (D3), n-hexane (D4), dichloromethane (D5)). The cells were incubated with 100 and 125 μg/mL of the fractions 24 hours. Combination of fluorescence microscopy, enzyme assays, Western blot analyses and flow cytometry were employed in the study. Results Treatment of the cells with MC fractions reduced Mitochondrial Membrane Potential (MMP) and intracellular ATP levels, while increasing reactive oxygen species levels without classical biochemical and morphological apoptotic features were seen. However, the fractions failed in upregulating either caspase-3 activation or cytochrome c release in the cancer cells. Conclusion: Overall, these results suggest that the cytotoxic effect of MC on the selected cancer cells is mediated by loss of mitochondrial function via loss of respiration leading to cell death rather than by the classical release of cytochrome c or caspase-3 activated apoptosis.