Antiproliferation and apoptosis induction of paeonol in HepG2 cells |
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Authors: | Xu Shu-Ping Sun Guo-Ping Shen Yu-Xian Wei Wei Peng Wan-Ren Wang Hua |
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Institution: | 1. Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Antiinflammatory and Immunological Pharmacology in Anhui Province, Key Laboratory of Research and Development of Chinese Medicine of Anhui province, Hefei 230032, Anhui Province, China 2. Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China 3. Department of Oncology, Provincial Hospital of Anhui, Hefei 230001, Anhui Province, China |
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Abstract: | AIM: 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. CONCLUSION: 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. |
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Keywords: | Paeonol Hepatocellular carcinoma Apoptosis Cell cycle Cisplatin Doxorubicin 5-fluorouracil Synergistic effect |
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