Involvement of p38 mitogen-activated protein kinase pathway in honokiol-induced apoptosis in a human hepatoma cell line (hepG2)
Involvement of p38 mitogen-activated protein kinase pathway in honokiol-induced apoptosis in a human hepatoma cell line (hepG2)
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DOI：
10.1111/j.1478-3231.2008.01767.x
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发表时间：
2008-11-01
影响因子：
6.7
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
--
作者：
Deng, Junfang;Qian, Yigang;Zheng, Shusen
背景：已知和厚朴酚具有抗肿瘤活性。本研究旨在评估和厚朴酚对 hepG2 肝细胞系的抗增殖潜力及其作用机制。方法：用0-40μg/ml浓度和厚朴酚处理hepG2细胞。和厚朴酚的细胞毒性作用通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物 (MTT) 测定法测定。通过流式细胞术评估细胞凋亡。 Western blots用于分析各种蛋白（procaspase-9、procaspase-3、cleaved caspase-3、细胞色素c、Bcl-2、Bax、Bad、Bcl-X-L和p38）的表达。结果：和厚朴酚通过降低 procaspase-3 和 -9 的表达以及增加活性 caspase-3 的表达来诱导细胞凋亡。 hepG2 细胞暴露于和厚朴酚会导致 Bcl-X-L 和 Bcl-2 表达下调，并导致线粒体细胞色素 c 释放到胞质中。此外，和厚朴酚激活 p38 丝裂原激活蛋白激酶 (MAPK) 途径，而 SB203580 对该途径的抑制可减少和厚朴酚诱导的细胞凋亡和 caspase-3 的激活。结论：和厚朴酚通过激活p38 MAPK通路，进而激活caspase-3，诱导hepG2人肝癌细胞凋亡。
Background: Honokiol has been known to have antitumour activity. This study was conducted to evaluate the antiproliferative potential of honokiol against the hepG2 heptocellular cell line and its mechanism of action. Methods: hepG2 cells were treated with honokiol of 0-40 mu g/ml concentration. The cytotoxic effect of honokiol was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis was evaluated by flow cytometry. Western blots were used to analyse the expression of various proteins (procaspase-9, procaspase-3, cleaved caspase-3, cytochrome c, Bcl-2, Bax, Bad, Bcl-X-L and p38). Results: Honokiol induced apoptosis with a decreased expression of procaspase-3 and -9 and an increased expression of active caspase-3. Exposure of hepG2 cells to honokiol resulted in the downregulation of Bcl-X-L and Bcl-2 expression and the release of mitochondrial cytochrome c to the cytosol. In addition, honokiol activated the p38 mitogen-activated protein kinase (MAPK) pathway, and the inhibition of this pathway by SB203580 reduced honokiol-induced apoptosis and activation of caspase-3. Conclusion: Honokiol induces apoptosis of hepG2 human hepatocellular carcinoma cells through activation of the p38 MAPK pathway, and, in turn, activation of caspase-3.