2α-Hydroxyursolic Acid Inhibited Cell Proliferation and Induced Apoptosis in MDA-MB-231 Human Breast Cancer Cells through the p38/MAPK Signal Transduction Pathway.

The mechanisms of action of 2α-hydroxyursolic acid in inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 human breast cancer cells were investigated. The antiproliferative activity and cytotoxicity were determined by the methylene blue assay. The expression of proteins was determined using Western blot. 2α-Hydroxyursolic acid significantly inhibited MDA-MB-231 cell proliferation, and no cytotoxicity was observed at concentrations below 30 μM. 2α-Hydroxyursolic acid significantly down-regulated expressions of TRAF2, PCNA, cyclin D1, and CDK4 and up-regulated the expressions of p-ASK1, p-p38, p-p53, and p-21. 2α-Hydroxyursolic acid induced apoptosis in MDA-MB-231 cells by significantly increasing the Bax/Bcl-2 ratio and inducing the cleaved caspase-3. Additionally, treatment of SB203580, a p38 MAPK specific inhibitor, reversed the inhibition of PCNA, cyclin D1, and Bcl-2 expression induced by 2α-hydroxyursolic acid in MDA-MB-231 cells. These results suggested that 2α-hydroxyursolic acid exhibited anticancer activity through the inhibition of cell proliferation and the induction of apoptosis by regulating the p38/MAPK signal transduction pathway.