Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines

Apoptotic effects of oleanolic acid (OA) and ursolic acid (UA) on human liver cancer HepG2, Hep3B, Huh7 and HA22T cell lines were examined. OA or UA at 2, 4, 8 micromol/L were used and their effects on cell viability, DNA fragmentation, mitochondrial membrane potential (MMP), activity of Na(+)-K(+)-ATPase, caspase-3 and caspase-8, cell adhesion, level of intercellular adhesion molecule (ICAM)-1 and vascular endothelial growth factor (VEGF) in these cell lines were determined. OA or UA treatments concentration-dependently decreased cell viability and increased DNA fragmentation in HepG2 and Hep3B cell lines (P<0.05). However, these two compounds reduced viability and increased DNA fragmentation in Huh7 cell only at 4 and 8 micromol/L (P<0.05). OA or UA treatments concentration-dependently lowered MMP in HepG2, Hep3B and HA22T cell lines (P<0.05). These two compounds also concentration-dependently diminished Na(+)-K(+)-ATPase activity and VEGF level in four test cell lines (P<0.05). Besides Huh7 cell, OA or UA treatments concentration-dependently elevated caspase-3 and caspase-8 activities in other three cell lines (P<0.05). Besides HA22T cell, these two compounds concentration-dependently inhibited cell adhesion and decreased ICAM-1 level in other three cell lines (P<0.05). These findings support that OA and UA are potent anti-cancer agents to cause apoptosis in these liver cancer cell lines.