p53-p66 shc /miR-21-Sod2 signaling is critical for the inhibitory effect of betulinic acid on hepatocellular carcinoma

•BA inhibited tumor growth and induced apoptosis in mice treated by DEN plus CCl4.•BA inhibited proliferation and induced apoptosis in hepatocellular carcinoma cells.•Increase of p53 was responsible for the pro-apoptotic and anti-tumor effect of BA.•Increase of p66shc and miR-21 and reduction of Sod2 was involved in anti-tumor effect of BA.•p53-p66shc/miR-21-Sod2 signaling is critical for the anti-tumor effect of BA.