title: Antiproliferation and apoptosis induction of paeonol in HepG2 cells.
abstract: OBJECTIVE
  To investigate the antiproliferative effect of paeonol (Pae) used alone or in combination with chemotherapeutic agents [cisplatin (CDDP), doxorubicin (DOX) and 5-fluorouracil (5-FU)] on human hepatoma cell line HepG2 and the possible mechanisms.
  
  
  METHODS
  The cytotoxic effect of drugs on HepG2 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphologic changes were observed by acridine orange (AO) fluorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry (FCM). Drug-drug interactions were analyzed by the coefficient of drug interaction (CDI).
  
  
  RESULTS
  Pae (7.81-250 mg/L) had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of (104.77 +/- 7.28) mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae (15.63, 31.25, 62.5 mg/L) was combined with CDDP (0.31-2.5 mg/L), DOX (0.16-1.25 mg/L), or 5-FU (12.5-100 mg/L) at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae (P < 0.01). Of the three different combinations, the sensitivity of cells to drugs was considerably different.
  
  
  CONCLUSIONS
  Pae had a significant growth-inhibitory effect on the human hepatoma cell line HepG2, which may be related to apoptosis induction and cell cycle arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2 cells, and the S phase arrest induced by Pae may be one of the mechanisms of these interactions.
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Antiinflammatory and Immunological Pharmacology in Anhui Province, Hefei 230032, Anhui Province, China.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Xu
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Sun
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Wan-Ren
authors.initials: WR
authors.lastname: Peng
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; C013638:paeonol