8-bromo-7-methoxychrysin-induced apoptosis of hepatocellular carcinoma cells involves ROS and JNK

作者: Xiao-Hong Yang , Xing Zheng , Jian-Guo Cao , Hong-Lin Xiang , Fei Liu

DOI: 10.3748/WJG.V16.I27.3385

关键词: CellPopulationCell cultureApoptosisCaspase 3Flow cytometryBiologyPropidium iodideMolecular biologyProgrammed cell deathGastroenterologyGeneral Medicine

摘要: AIM: To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin (BrMC) involve reactive oxygen species (ROS) generation and c-Jun N-terminal kinase (JNK) activation in human hepatocellular carcinoma cells (HCC). METHODS: HepG2, Bel-7402 L-02 cell lines were cultured vitro effects BrMC evaluated by flow cytometry (FCM) after propidium iodide (PI) staining, caspase-3 activity using enzyme-linked immunosorbent assay (ELISA), DNA agarose gel electrophoresis. ROS production was FCM dichlorodihydrofluorescein diacetate (DCHF-DA) probe labeling. The phosphorylation level JNK protein analyzed Western blotting. RESULTS: PI staining showed a dose-dependent increase percentage sub-G1 population (P < 0.05), reaching 39.0% ± 2.8% HepG2 48 h treatment with at 10 μmol/L. potency to (32.1% 2.6%) found be more effective than lead compound, chrysin (16.2% 1.6% for 11.0% 1.3% cell) 40 μmol/L similar 5-flurouracil (33.0% 2.1% 29.3% 2.3% cells) had little effect on embryo liver cells, 5.4% 1.8%. Treatment also increased levels active caspase-3, concentration-dependent manner. z-DEVD-fmk, caspase-3-specific inhibitor, prevented caspase-3. resulted formation ladder. (10 μmol/L) mean fluorescence intensity DCHF-DA from 7.2 1.12 0 79.8 3.9 3 89.7 4.7 6 h. did not affect cells. failed induce death pretreated N-acetylcysteine mmol/L). In addition, treated (2.5, 5.0, 10.0 12 h, observed. Peak occurred post-treatment this persisted up 24 expression phosphorylated BrMC-treated inhibited SP600125 pre-treatment, but GW9662 no effect. substantially reduced BrMC-induced attenuated induction BrMC. CONCLUSION: induces apoptosis HCC sustained activation.

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