BETULINIC ACID-MEDIATED CELL CYCLE ARREST, DECREASE IN MITOCHONDRIAL MEMBRANE POTENTIAL AND SUCCINATE DEHYDROGENASE ACTIVITY IN MURINE ASCITES DALTON’S LYMPHOMA

Surya Bali Prasad*, Anamika Bhaumik, Javadi Monisha, Arun B. Gurung, Ajaikumar B. Kunnumakkara, Atanu Bhattacharjee and Rajesh Prasad

ABSTRACT

Betulinic acid is a pentacyclic triterpenoid originally isolated from the bark of the white birch Betula pubescens, from which it got its name. Betulinic acid exhibits cytotoxicity in several cancer cell lines and the antitumor potential of betulinic acid against murine ascites Dalton’s lymphoma has been earlier reported by us. Present studies were undertaken to further explore and evaluate the possible mechanism of antitumor activity of betulinic acid with reference to cell cycle analysis, changes in mitochondrial membrane potential and succinate dehydrogenase activity in Dalton’s lymphoma cells. Cell cycle analysis using flow cytometry, changes in mitochondrial membrane potential and succinate dehydrogenase activity in Dalton’s lymphoma cells were determined after betulinic aid treatment. In silico molecular docking study was done to scrutinize possible interaction of succinate dehydrogenase with betulinic acid. Betulinic acid treatment caused cell cycle arrest at S phase and also decreased mitochondrial membrane potential and succinate dehydrogenase activity in Dalton’s lymphoma cells. Molecular docking study revealed the strong binding affinity of betulinic acid with succinate dehydrogenase. The decreased mitochondrial membrane potential and inhibition in succinate dehydrogenase activity in Dalton’s lymphoma tumor cells after betulinic acid treatment may lead to the development of mitochondrial dysfunction and could be contributing to tumor cells death and should be imperative in its antitumor activity. It is suggested that mitochondria-targeted agents such as betulinic acid holds great promise as a novel anticancer drug.

Keywords: Betulinic acid, Dalton’s lymphoma. cell cycle, mitochondrial membrane potential, succinate dehydrogenase.