Down regulation of differentiated embryonic chondrocytes 1 (DEC1) is involved in 8-methoxypsoralen-induced apoptosis in HepG2 cells

Down regulation of differentiated embryonic chondrocytes 1 (DEC1) is involved in 8-methoxypsoralen-induced apoptosis in HepG2 cells
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分化胚胎软骨细胞 1 (DEC1) 的下调参与 8-甲氧基补骨脂素诱导的 HepG2 细胞凋亡

DOI:
10.1016/j.tox.2012.06.022
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发表时间:
2012-11-15
期刊:
影响因子:
4.5
通讯作者:
Yang, Jian
Yang, Jian
中科院分区:
医学3区
文献类型:
--
作者:
Peng, Yan;Liu, Wei;Yang, Jian

文献摘要

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8-甲氧补骨脂素(8-MOP)是一种天然化合物,与紫外线结合后可有效调节表皮细胞的生长和分化。然而,很少有关于8-MOP单独对细胞凋亡的贡献的信息。在这项研究中,我们评估了8-MOP,独立于其光活化,诱导人肝癌HepG 2细胞凋亡。我们提供了8-MOP诱导细胞凋亡的分子解释。在HepG 2细胞中,8-MOP处理以剂量依赖性和时间依赖性方式诱导细胞凋亡。8-MOP在48和72 h的IC 50值分别为8.775和5.398 μ M。进一步的研究表明,8-MOP可降低caspase-3、caspase-8和caspase-9的表达,增加Bax/Bc 1 -2的比值,降低survivin的表达。此外,8-MOP减少分化的胚胎软骨细胞基因1(DEC 1)。过表达DEC 1可部分拮抗8-MOP诱导的细胞凋亡。DEC 1过表达可部分阻断8-MOP诱导的Survivin表达下降和caspase-3的激活。因此,DEC 1的下调参与了8-MOP诱导的HepG 2细胞凋亡。在此,证明了DEC 1在8-MOP处理的HepG 2细胞中具有抗凋亡作用。这些发现为8-MOP作为抗肿瘤药物用于癌症治疗提供了更多的依据。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
8-Methoxypsoralen (8-MOP), a naturally occurring compound, is a potent modulator of epidermal cell growth and differentiation in combination with ultraviolet light. However, there is little information on 8-MOP contribution to cell apoptosis alone. In the study, we evaluated 8-MOP, independently of its photoactivation, induced apoptosis in human hepatocellular carcinoma HepG2 cells. And we provide a molecular explanation linking 8-MOP to induce apoptosis. In HepG2 cells, treatment with 8-MOP induced the cell apoptosis in both dose-dependent and time-dependent manners. IC50 values of 8-MOP were 8.775, 5.398 mu M for 48 and 72 h, respectively. Further study showed that 8-MOP decreased the procaspase-3, procaspase-8, and procaspase-9, increased the ratio of Bax/Bc1-2 and decreased the survivin. Moreover, 8-MOP decreased differentiated embryonic chondrocyte gene1 (DEC1). Overexpression of DEC1 antagonized partially apoptosis induced by 8-MOP. And overexpression of DEC1 abolished the decrease of survivin and the activation of caspase-3 induced by 8-MOP partially. So, down regulation of DEC1 is involved in 8-MOP-induced apoptosis in HepG2 cells. Here, it is demonstrated that DEC1 possesses antiapoptotic effects in 8-MOP-treated HepG2 cells. The findings provide more of a basis for 8-MOP as an anti-tumor agent in cancer therapy. (c) 2012 Elsevier Ireland Ltd. All rights reserved.