title: Oleanolic acid and ursolic acid inhibit proliferation in transformed rat hepatic oval cells.
abstract: OBJECTIVE
  To investigate H2O2-induced promotion proliferation and malignant transformation in WB-F344 cells and anti-tumor effects of ursolic acid (UA) and oleanolic acid (OA).
  
  
  METHODS
  WB-F344 cells were continuously exposed to 7 x 10(-7) mol/L H2O2 for 21 d. Observations of cell morphology, colony formation rates, flow cytometric analysis of cell cycle changes and aneuploidy formation indicated that H2O2 was able to induce malignant transformation of WB-F344 cells. We treated malignantly transformed WB-F344 cells with 4 μmol/L OA or 8 μmol/L UA for 72 h and analyzed the cell cycle distribution by flow cytometry.
  
  
  RESULTS
  MTT assay showed that 7 x 10(-7) mol/L H2O2 decreased G1 phase subpopulation from 73.8% to 49.6% compared with the control group, and increased S phase subpopulation from 14.5% to 31.8% (P < 0.05 vs control group). Cell morphology showed that nucleus to cytoplasm ratio increased, many mitotic cells, prokaryotes and even tumor giant cells were shown in H2O2-induced WB-F344 cells. Fluorescence activated cell sorting analysis showed that WB-F344 cell aneuploidy increased to 12% following H2O2 treatment. Flow cytometric analysis of the transformed WB-F344 cells following treatment with OA (4 μmol/L) and UA (8 μmol/L) showed that OA increased G1 subpopulation to 68.6%, compared to 49.7% in unexposed cells. UA increased G1 subpopulation to 67.4% compared to 49.7% in unexposed cells (P < 0.05 vs H2O2 model group).
  
  
  CONCLUSIONS
  H2O2 causes the malignant transformation of WB-F344 cells. OA and UA exert anti-tumor effects by inhibiting the proliferation in malignantly transformed WB-F344 cells.
authors.affiliation: Yu-Ying Han, Department of Medical Genetics, Capital Medical University, Beijing 100069, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Han
authors.affiliation: Yu-Ying Han, Department of Medical Genetics, Capital Medical University, Beijing 100069, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Xue
authors.affiliation: Yu-Ying Han, Department of Medical Genetics, Capital Medical University, Beijing 100069, China.
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Shi
authors.affiliation: Yu-Ying Han, Department of Medical Genetics, Capital Medical University, Beijing 100069, China.
authors.forename: Peng-Yan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Yu-Ying Han, Department of Medical Genetics, Capital Medical University, Beijing 100069, China.
authors.forename: Xin-Rui
authors.initials: XR
authors.lastname: Wu
authors.affiliation: Yu-Ying Han, Department of Medical Genetics, Capital Medical University, Beijing 100069, China.
authors.forename: Xue-Jiang
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D009828:Oleanolic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D006861:Hydrogen Peroxide; D009828:Oleanolic Acid; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Hepatocarcinogenesis; Malignant transformation; Oleanolic acid; Oxidative stress; Ursolic acid