Investigation of Genotoxicity Induced by a Potent Bitter Gourd (Momordica Charantia) in Breast Cancer Cells

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological and Environmental Sciences

Date of Award

9-1-2026

Abstract

Breast cancer is still the number one cause of cancer-linked mortality in women worldwide although there have been advancements in treatment options. Resistance to therapy and toxicity associated with conventional treatments continue to call for the development of alternative anticancer strategies with improved selectivity and reduced side effects. Momordica charantia (bitter gourd/bitter melon), a phytochemical-rich medicinal plant commonly consumed in Asia has demonstrated promising anticancer activity in several cancer models. However, the precise mechanism underlying bitter gourd-induced cytotoxicity in breast cancer remains underexplored. In this study, we investigated the mechanism of anticancer effects induced by a potent bitter gourd cultivar in breast cancer cells. We also evaluated whether bitter gourd promotes ROS-mediated genotoxicity leading to cell death. MCF-7/Vector, MCF-7/G1P3 and MDA-MB-231 cells were administered with aqueous extracts of Indian heirloom (HI), Chinese (Mara) and U.S.-grown hybrid (HB) bitter gourd. Colony formation assay was performed to determine antiproliferative and cytotoxic activity and identify the most potent extract. Cell cycle analysis, ROS detection assay, TMRM staining, DAPI staining, comet assay, NAC reversal experiments and western blot analysis were used to assess Sub-G1 accumulation, oxidative stress, mitochondrial membrane potential, nuclear deformation, DNA damage, ROS involvement and apoptotic pathway activation, respectively. HI demonstrated the greatest antiproliferative and cytotoxic activity across all the cell lines used. MDA-MB-231 were very susceptible to all extracts, whereas MCF-7/G1P3 cells showed relative resistance. The absence of cleaved caspase-3 expression in treated MDA-MB-231 cells suggested that HI-induced cell death may occur predominantly through caspase-independent mechanisms. HI increased intracellular ROS production, induced mitochondrial membrane depolarization, increased Sub-G1 accumulation and promoted nuclear deformation in breast cancer cells. HI increased DNA damage in MCF-7/Vector, MCF-7/G1P3 and MDA-MB-231 cells. NAC attenuated HI-induced nuclear deformation and DNA damage in MCF-7 cells, suggesting ROS-mediated genotoxicity. In contrast, NAC did not reverse HI-induced nuclear deformation or DNA damage in MDA-MB-231 cells. This indicated that additional ROS-independent mechanisms may contribute to genotoxicity in this cell line.

Advisor

Venugopalan Cheriyath

Subject Categories

Biology | Life Sciences

Link to Full Text

Share

COinS