title: Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro.
abstract: Hypericin, an antidepressant and antiviral agent being evaluated in phase 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 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and clonogenic assay in three human glioblastoma cell lines, U87-MG, A-172, and T98G, and a low-passage malignant glioma culture, 93-492. At a concentration of 5 microM, hypericin inhibited these cells slightly but caused significant radiosensitization (e.g., the cell survival rate after the radiation treatment was 50.2 and 26.0% in cells treated with 6 Gy and 6 Gy plus 5 microM hypericin in U87-MG cells, respectively; P = 0.0285). Hypericin also enhanced the radiosensitivity significantly in the low-passage glioma 93-492 cells. These findings suggest that hypericin represents a potential new agent in combination with radiation therapy of malignant gliomas.
authors.affiliation: Departments of Neurological Surgery, robiolology, and Radiation Oncology, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Anker
authors.forename: R E
authors.initials: RE
authors.lastname: Law
authors.forename: D R
authors.initials: DR
authors.lastname: Hinton
authors.forename: R
authors.initials: R
authors.lastname: Gopalakrishna
authors.forename: Q
authors.initials: Q
authors.lastname: Pu
authors.forename: U
authors.initials: U
authors.lastname: Gundimeda
authors.forename: M H
authors.initials: MH
authors.lastname: Weiss
authors.forename: W T
authors.initials: WT
authors.lastname: Couldwell
mesh_terms: D000873:Anthracenes; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin; D011493:Protein Kinase C