HYPERICIN - A POTENTIAL ANTIGLIOMA THERAPY

HYPERICIN, A POLYCYCLIC aromatic dione isolated from plants, is presen tly being clinically evaluated as an antiviral agent in the treatment of human immunodeficiency virus (HIV) infection. In addition, it is kn own to be a potent protein kinase C inhibitor. To evaluate its potenti al as an inhibitor of glioma growth, an established (U87) and low-pass age glioma line (93-492) were treated with hypericin in tissue culture for a period of 48 hours after passage. Hypericin inhibited the gliom a 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-p assage line 93-492, a concentration of hypericin of 10 mu mol/L produc ed 62 and 76% decreases in [H-3]thymidine uptake, respectively). Becau se the reported inhibitory effects of protein kinase C are enhanced by visible light, [H-3]thymidine uptake was measured in both the presenc e and the absence of visible light. In glioma line A172, the presence of light slightly increased the inhibitory effect of hypericin. Moreov er, an apoptosis (i.e., programmed cell death) assay was performed to determine whether the treatment of glioma cells with hypericin was cyt ostatic or cytocidal. Cells were harvested, and purified deoxyribonucl eic acid (DNA) was analyzed by agarose gel electrophoresis. DNA from c ells treated with hypericin for 48 hours exhibited a classical ''ladde r'' pattern of oligonucleosome-sized fragments characteristic of apopt osis. These data suggest that the proven safe drug hypericin may have potential as an antiglioma agent; we suggest clinical trials.