title: Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines.
abstract: 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.
authors.affiliation: Department and Graduate Program of BioIndustry Technology, Dayeh University, Changhua County, Taiwan, ROC.
authors.forename: Sheng-lei
authors.initials: SL
authors.lastname: Yan
authors.forename: Chun-yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Shwu-tzy
authors.initials: ST
authors.lastname: Wu
authors.forename: Mei-chin
authors.initials: MC
authors.lastname: Yin
mesh_terms: 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
chemical_list: 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