ENHANCEMENT OF RADIOSENSITIVITY IN HUMAN-MALIGNANT GLIOMA-CELLS BY HYPERICIN IN-VITRO

Hypericin, an antidepressant and antiviral agent being evaluated in ph ase I and II trials for patients with HIV infection, is known to be a potent protein kinase C inhibitor, We have investigated its effects on cellular response to radiation via a tetrazolium-formazan cell growth rate assay using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium b romide and clonogenic assay in three human glioblastoma cell lines, U8 7-MG, A-172, and T98G, and a low-passage malignant glioma culture, 93- 492. At a concentration of 5 mu M hypericin inhibited these cells slig htly but caused significant radiosensitization (e.g,, the cell surviva l rate after the radiation treatment was 50.2 and 26.0% in cells treat ed with 6 Gy and 6 Gy plus 5 mu M hypericin in U87-MG cells, respectiv ely; P = 0.0285), Hypericin also enhanced the radiosensitivity signifi cantly in the low-passage glioma 93-492 cells, These findings suggest that hypericin represents a potential new agent in combination with ra diation therapy of malignant gliomas.