Betulinic Acid-Induced Cytotoxicity in Human Breast Tumor Cell Lines MCF-7 and T47D and its Modification by Tocopherol

Betulinic acid (BA) has been shown to cause apoptosis in neuroblastoma and melanoma cell lines. We evaluated the cytotoxicity of BA in two breast cancer cell lines MCF-7 and T47D differing in their p53 status. Treatment with BA resulted in a dose dependent inhibition of cell proliferation and induction of apoptosis. This indicates p53-independent apoptotic pathway, because response of both p53 mutant and wild type cell line were found unaffected after treatment with pifithrin-alpha, an inhibitor of p53. Cells were significantly protected when treated by tocopherol suggesting involvement of membrane centered lipid peroxidation-mediated mechanism in BA-induced apoptosis.