Couldwell W T, Gopalakrishna R, Hinton D R, He S, Weiss M H, Law R E, Apuzzo M L, Law R E
Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles.
Neurosurgery. 1994 Oct;35(4):705-9; discussion 709-10. doi: 10.1227/00006123-199410000-00017.
Hypericin, a polycyclic aromatic dione isolated from plants, is presently being clinically evaluated as an antiviral agent in the treatment of human immunodeficiency virus (HIV) infection. In addition, it is known to be a potent protein kinase C inhibitor. To evaluate its potential as an inhibitor of glioma growth, an established (U87) and low-passage glioma line (93-492) were treated with hypericin in tissue culture for a period of 48 hours after passage. Hypericin inhibited the glioma growth in a dose-related manner, with a marked inhibition of growth in the low-micromolar concentration range (e.g., in line U87 and low-passage line 93-492, a concentration of hypericin of 10 mumol/L produced 62 and 76% decreases in [3H]thymidine uptake, respectively). Because the reported inhibitory effects of protein kinase C are enhanced by visible light, [3H]thymidine uptake was measured in both the presence and the absence of visible light. In glioma line A172, the presence of light slightly increased the inhibitory effect of hypericin. Moreover, an apoptosis (i.e., programmed cell death) assay was performed to determine whether the treatment of glioma cells with hypericin was cytostatic or cytocidal. Cells were harvested, and purified deoxyribonucleic acid (DNA) was analyzed by agarose gel electrophoresis. DNA from cells treated with hypericin for 48 hours exhibited a classical "ladder" pattern of oligonucleosome-sized fragments characteristic of apoptosis. These data suggest that the proven safe drug hypericin may have potential as an antiglioma agent; we suggest clinical trials.
金丝桃素是一种从植物中分离出来的多环芳香二酮，目前正在进行临床评估，作为一种抗病毒药物用于治疗人类免疫缺陷病毒（HIV）感染。此外，已知它是一种有效的蛋白激酶C抑制剂。为了评估其作为胶质瘤生长抑制剂的潜力，在传代后，将已建立的（U87）和低传代胶质瘤细胞系（93-492）在组织培养中用金丝桃素处理48小时。金丝桃素以剂量相关的方式抑制胶质瘤生长，在低微摩尔浓度范围内有明显的生长抑制作用（例如，在U87细胞系和低传代细胞系93-492中，金丝桃素浓度为10 μmol/L时，[3H]胸苷摄取分别减少62%和76%）。由于据报道蛋白激酶C的抑制作用在可见光下会增强，因此在有和没有可见光的情况下都测量了[3H]胸苷摄取。在胶质瘤细胞系A172中，光照的存在略微增强了金丝桃素的抑制作用。此外，进行了凋亡（即程序性细胞死亡）检测，以确定用金丝桃素处理胶质瘤细胞是具有细胞生长抑制作用还是细胞杀伤作用。收获细胞，并用琼脂糖凝胶电泳分析纯化的脱氧核糖核酸（DNA）。用金丝桃素处理48小时的细胞的DNA呈现出典型的凋亡特征性寡核小体大小片段的“梯形”模式。这些数据表明，已证实安全的药物金丝桃素可能具有作为抗胶质瘤药物的潜力；我们建议进行临床试验。
