Hypericin inhibits cell growth and induces apoptosis in retinal pigment epithelial cells: Possible involvement of protein kinase C
Hypericin inhibits cell growth and induces apoptosis in retinal pigment epithelial cells: Possible involvement of protein kinase C
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DOI：
10.3109/02713689609007619
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发表时间：
1996-03-01
影响因子：
2
通讯作者：
Ryan, SJ
中科院分区：
文献类型：
--
作者：
Harris, MS;Sakamoto, T;Ryan, SJ
增生性玻璃体视网膜病变（PVR）是以视网膜色素上皮（RPE）细胞在玻璃体腔内的增殖和迁移为特征的。金丝桃素这种药物已经在临床上用作抗抑郁剂，它已经显示出作为抗病毒药和抗病毒剂的前景。为了研究金丝桃素在PVR中的治疗潜力，我们在含有0.5至5 μ M金丝桃素的各种血清浓度的标准培养基中孵育RPE细胞。在一些实验中，我们研究了金丝桃素与RPE生长刺激细胞因子肿瘤坏死因子α（TNF-α）结合的作用。在1%和5%血清中，发现对RPE细胞增殖的剂量依赖性抑制，IC 50值分别为0.7 μ M和3.3 μ M，即使与TNF-α结合，金丝桃素也抑制RPE增殖，IC 50值为1.5 μ M。该药物抑制PKC活性与2.5 μ M剂量处理的细胞中的72%，30分钟后，180分钟后，由100%。最后，金丝桃素诱导RPE细胞进行凋亡细胞死亡，所示的DNA梯状的存在。这些结果表明，金丝桃素可能有潜力作为PVR的治疗药物，其抗增殖和凋亡的作用在体外的RPE细胞部分介导的PKC。
Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) cells in the vitreous cavity. The drug hypericin, which is already in clinical use as an antidepressant, has shown promise as an antiviral and antineoplastic agent. To investigate the therapeutic potential of hypericin in PVR, we incubated RPE cells in standard medium with various serum concentrations containing 0.5 to 5 mu M hypericin. In some experiments we studied the effects of hypericin in conjunction with the RPE growth stimulating cytokine tumor necrosis factor alpha (TNF-alpha). Dose-dependent inhibition of RPE cell proliferation with IC50 values of 0.7 mu M and 3.3 mu M in 1% and 5% serum respectively, was found. Even in conjunction with TNF-alpha, hypericin inhibited RPE proliferation with an IC50 value of 1.5 mu M. The drug inhibited PKC activity in cells treated with a 2.5 mu M dose by 72% after 30 min and by 100% after 180 min. Finally, hypericin induced RPE cells to undergo apoptotic cell death, as shown by the presence of DNA laddering. These results suggest that hypericin may have potential as a therapeutic drug for PVR and that its antiproliferative and apoptotic effects on RPE cells in vitro are in part mediated by PKC.