Aqueous Vernomia amygdalina Extracts Alter MCF-7 Cell Membrane Permeability and Efflux

Breast cancer is the second leading cause of cancer related deaths of women in the United States. Several treatment strategies have been developed over the past decade to reduce cancer morbidity and mortality rates. While mortality rates have declined in some ethnic populations, the overall cancer incidence continues to grow. Hence, chemotherapeutic agents are needed to improve cancer treatment outcome. Previous studies show that low concentrations (microgram/ml) of water-soluble leaf extracts of a Nigerian edible plant, V. amygdalina (VA), potently retard the proliferative activities of estrogen receptor positive (ER+) human breast cancerous cells (MCF-7) cells in vitro in a concentration-dependent fashion. The anti-proliferative activities of VA are extracellular signal-regulated kinases 1/2 (ERKs 1/2)-dependent. Cell culture and animal model studies, conducted by other investigators using other plant extracts, have also revealed that plant extract components called thionins may be responsible for their anticancer activities. These thionins are believed to interact with the cells in ways that compromise membrane potential/permeability resulting in the alteration of efflux, cytosolic activities, and subsequent cell death. Therefore, we hypothesized that VA exposure may compromise cell membrane as another mode of action to elicit its anticancer activities in MCF-7 cells. The exposure of cells to VA decreased [(3)H]thymidine uptake in a concentration-dependent (0, 30, and 100 μg/ml VA) manner (p < 0.05) but increased [(3)H]thymidine release, expressed as percent of [(3)H]thymidine incorporated, into the medium (p < 0.05). The amount of [(3)H]thymidine released into the medium was 1.7, 7.4, and 11.0 % for 0, 30, and 100 μg/ml VA respectively. Thus suggesting the membranes in VA-treated cells were compromised in a concentration-dependent fashion.