Biochemical and mitochondrial membrane potential changes relating to betulinic acid-mediated anticancer activity in murine ascites Dalton's lymphoma

Abstract

BackgroundBetulinic acid, a naturally occurring pentacyclic triterpenoid is found in a variety of plants. A range of biological properties including anticancer activity has been reported for betulinic acid. Changes in glutathione and some glutathione-related enzymes and mitochondrial membrane potential have not been explored relating to the anticancer activity of betulinic acid against murine ascites Dalton's lymphoma.The present study was undertaken to examine betulinic acid-mediated changes in glutathione and mitochondrial membrane potential in murine malignant ascites Dalton's lymphoma cells to identify their involvement as the possible mechanism in its anticancer activity. Method: The anticancer efficacy of betulinic acid was explored as a percentage increase in the life span (ILS) of the tumor-bearing mice. Betulinic acid-mediated changes in glutathione level, glutathione-related enzymes, succinate dehydrogenase activity, and mitochondrial membrane potential were determined in Dalton's lymphoma cells using well-established methods. In silico molecular docking study was done to know the binding affinity of betulinic acid with selected glutathione related enzymes and succinate dehydrogenase. Results: Betulinic acid significantly increased the life span of ascites Dalton's lymphoma-bearing hosts, thus exhibiting anticancer potential. The treatment caused a decrease in glutathione and glutathione-related enzymatic activities in DL cells. In silico molecular docking analysis revealed that betulinic acid illustrates good binding affinity with glutathione-related enzymes indicating its inhibitory potentials. Further, a decrease in mitochondrial membrane potential and succinate dehydrogenase activity was also noted after treatment. Conclusions: Betulinic acid-mediated decrease in glutathione in DL cells may hamper cellular antioxidant defense potential, which could play an important causative role in exerting its anticancer activity. Further, a concurrent decrease in mitochondrial membrane potential and succinate dehydrogenase activity is also important in its anticancer activity.