Treatment with Momordica charantia Fractions Disrupts Energy Metabolism and Elevated Reactive Oxygen Species’ Generation in Human Lung and Breast Cancer Cell Lines

Abstract

The mechanism of action of mitochondrial targeted anti‐cancer drugs relies on their ability to disrupt the energy producing systems of cancer cell mitochondria. Momordica charantia (MC), an acclaimed anticancer plant in folk medicine, is here investigated for the probable mechanism by which it kills cancer cells. The ethyl acetate (D3), n‐hexane (D4) and dichloromethane (D5) fractions were obtained from the Crude Water‐Soluble extract (CWSE) of MC via solvent partitioning and then administered on MDA‐MB 436 and A549 cells at 100 and 125 μg/mL for 24 h. Cytofluorometric techniques, using TMRM and H2DCF‐DA as fluorescent probes were employed to assess the effect of MC on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation respectively, while ATP levels were measured using the luciferin‐luciferase reaction. Mean respiring cell numbers obtained from Dot graphs and Histograms were further analyzed, yielding significant (P<0.05) MMP depressions only at 125μg/mL in both MDA‐MB 436 (43.08±2.33) and A549 (24.84±2.51) cells treated with D3 in comparison with untreated cells (175.8±6.13 and 131.7±11.21 respectively). In the same vein, only MDA‐MB 436 cells treated with D3 and D5 at 100 and 125 μg/mL significantly elevated ROS levels in comparison with untreated (100.0±2.16) cells; the highest generation being 332.1±3.20, seen in D3‐treated cells at 125 μg/mL. Furthermore, all fractions (D3‐D5) tested on A549 cells at 100μg/mL and 125μg/mL generated significantly higher levels of ROS compared with the untreated (42±4.50) group. The highest observed levels of generated ROS were seen at 125μg/mL in the D5‐treated cells (536±4.00). For intracellular ATP generation, significant (P<0.05) depletion was observed in both MDA‐MB 436 cells [only at 125μg/mL of D3 (80.63±4.70) compared with the control group (106.7±5.69)] and A549 cells [D3 at 125 μg/mL (43.68±0.13) < D5 at 125 μg/mL (52.56±4.16) < D3 at 100 μg/mL (59.84±5.39) compared with the control group (98.57±0.66)]. On the whole, this study suggests that the tested fractions of MC induced a mitochondrial‐dependent cell death in selected cancer cell lines.Support or Funding InformationOrganization for Women in Science for the Developing World (OWSD) and Swedish International Development Cooperation Agency (SIDA)