Growth-inhibitory and differentiation-inducing activity of dimethylformamide in cultured human malignant glioma cells.
OBJECTIVE
To determine the growth-inhibitory and differentiation-inducing activity of dimethylformamide (DMF) on a human glioma cell line (SHG-44). DMF is a type of polar solvent and a potent differentiation-inducing agent in many kinds of human solid tumors, yet its effect on human glioma remains unclear.


METHODS
The effects of DMF on cell proliferation using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell cycle distribution (with flow cytometry), colony-forming 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-forming 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 G0/G1 phases was observed in DMF-treated (0.5 and 1.0%) cells, 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-shaped to large polygonal and flattened stellate cells with multiple slender processes. These cells were still tumorigenic in athymic nude mice, but the growth of xenografts was remarkably reduced, especially in the 1.0% DMF-treated group. The expression of glial fibrillary acidic protein was notably increased by DMF (0.5 and 1.0%). Washout experiments revealed that the effects of DMF on cell proliferation and cell cycle distribution were reversible.


CONCLUSIONS
Our results suggest that DMF drove the SHG-44 cells to a more mature phenotype with inhibited growth.
Li
X N
XN
Department of Neurosurgery, Second Affiliated Hospital, Suzhou Medical College, People's Republic of China.
Du
Z W
ZW
Huang
Q
Q
Wu
J Q
JQ
D000328:Adult; D000818:Animals; D001254:Astrocytoma / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002461:Cell Line, Transformed; D004126:Dimethylformamide / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D004126:Dimethylformamide