GROWTH-INHIBITORY AND DIFFERENTIATION-INDUCING ACTIVITY OF DIMETHYLFORMAMIDE IN CULTURED HUMAN-MALIGNANT GLIOMA-CELLS

OBJECTIVE: To determine the growth-inhibitory and differentiation-indu cing activity of dimethylformamide (DMF) on a human glioma cell line ( SHG-44). DMF is a type of polar solvent and a potent differentiation-i nducing agent in many kinds of human solid tumors, yet its effect on h uman glioma remains unclear. METHODS: The effects of DMF on cell proli feration using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell cycle distribution (with flow cytometry), colony-f orming efficiency in double-layer soft agar, tumorigenicity in athymic nude mice, morphological changes, and glial fibrillary acidic protein expression were studied. RESULTS: At dose ranges of 0.25, 0.5, 0.75, and 1.0%, DMF caused a dose-dependent proliferation inhibitory effect in monolayers and a marked dose-dependent suppression of colony-formin g efficiency in double-layer soft agar with a complete loss of colony- forming ability in cells exposed to 0.75 and 1.0% DMF. Accumulation of cells in G(0)/C-1 phases was observed in DMF-treated (0.5 and 1.0%) c ells, also in a dose-dependent manner. SHG-44 cells exposed to DMF (0. 5 and 1.0%) for 15 days changed morphologically from small spindle-sha ped to large polygonal and flattened stellate cells with multiple slen der processes. These cells were still tumorigenic in athymic nude mice , but the growth of xenografts was remarkably reduced, especially in t he 1.0% DMF-treated group. The expression of glial fibrillary acidic p rotein was notably increased by DMF (0.5 and 1.0%). Washout experiment s revealed that the effects of DMF on cell proliferation and cell cycl e distribution were reversible. CONCLUSION: Our results suggest that D MF drove the SHC-44 cells to a more mature phenotype with inhibited gr owth.