Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Toxicology. 2012 Nov 15;301(1-3):58-65. doi: 10.1016/j.tox.2012.06.022. Epub 2012 Jul 11.
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. IC(50) values of 8-MOP were 8.775, 5.398 μM 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/Bcl-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 anti-apoptotic 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.
8-甲氧基补骨脂素(8-MOP)是一种天然存在的化合物,与紫外线联合使用时,能有效调节表皮细胞的生长和分化。然而,关于 8-MOP 单独诱导细胞凋亡的信息却很少。在本研究中,我们评估了 8-MOP 在不进行光活化的情况下,对人肝癌 HepG2 细胞凋亡的诱导作用。并提供了一个分子解释,将 8-MOP 与诱导细胞凋亡联系起来。在 HepG2 细胞中,8-MOP 以剂量和时间依赖的方式诱导细胞凋亡。8-MOP 的 IC50 值分别为 48 和 72 h 时的 8.775 和 5.398 μM。进一步的研究表明,8-MOP 降低了 procaspase-3、procaspase-8 和 procaspase-9 的水平,增加了 Bax/Bcl-2 的比值,降低了 survivin 的水平。此外,8-MOP 降低了分化胚胎软骨细胞基因 1(DEC1)的表达。DEC1 的过表达部分拮抗了 8-MOP 诱导的细胞凋亡。并且,DEC1 的过表达部分消除了 8-MOP 诱导的 survivin 减少和 caspase-3 激活。因此,DEC1 的下调参与了 8-MOP 诱导的 HepG2 细胞凋亡。本研究证明,DEC1 在 8-MOP 处理的 HepG2 细胞中具有抗凋亡作用。这些发现为 8-MOP 作为癌症治疗中的抗肿瘤药物提供了更多的依据。