METHYLENE-BLUE INDUCES CYTOTOXICITY IN HUMAN BRAIN-TUMOR CELLS

Methylene blue (MB), a known inhibitor of guanylyl cyclase, induced cy totoxicity in SK-N-MC human neuroblastoma and U-373 MG human astrocyto ma cells in a dose-dependent manner. MB did not significantly alter ce llular levels of cGMP in both cells. 8-Br cGMP, a membrane-permeable a nalogue of cGMP, did not decrease MB-induced cytotoxicity, indicating that cGMP may not be a major target of the cytotoxic action of MB. How ever, hydroxyl;radical scavengers or intracellular Ca2+ modulators eff ectively blocked the MB-induced cytotoxicity. These results suggest th at hydroxyl radical and intracellular Ca2+ may have an important invol vement in the cytotoxic action of MB. These results further suggest th at the treatment with MB may be useful for the therapeutic application s of human brain tumors.