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.
Yan
Sheng-lei
SL
Department and Graduate Program of BioIndustry Technology, Dayeh University, Changhua County, Taiwan, ROC.
Huang
Chun-yin
CY
Wu
Shwu-tzy
ST
Yin
Mei-chin
MC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D009362:Neoplasm Metastasis / Q000473:pathology; D009828:Oleanolic Acid / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D020169:Caspases; D004396:Coloring Agents; D018799:Intercellular Adhesion Molecule-1; D009828:Oleanolic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; D000097245:Ursolic Acid; C022616:thiazolyl blue