INDUCTION OF GLIOMA CELL-DEATH BY 1,25(OH)(2) VITAMIN-D-3 - TOWARDS AN ENDOCRINE THERAPY OF BRAIN-TUMORS

The secosteroid 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is the majo r biologically active metabolite of vitamin D. Antitumor activity of t his hormone has been observed on several cell lines and on breast canc er in vivo. The purpose of this in vitro study was to determine the po ssible effect of 1,25(OH)(2)D-3 on glioma cells. Two glioma cell lines from rat (C6) or human (GHD) origin were cultured in the presence of 1,25(OH)(2)D-3. The sensitivity of these cells to 1,25(OH)(2)D-3 was a ssessed with a colorimetric MTT assay. A cytotoxic effect of 1,25(OH)( 2)D-3 was detected at concentrations around 10(-8) M. A lag period of 3 days was required between the onset of the treatment and the observa tion of the effects. However, the continuous presence of 1,25(OH)(2)D- 3 is not required since cell death occurred even when C6 cells were ch allenged for 24 hr with 1,25(OH)(2)D-3 and then cultured in the absenc e of the hormone. In addition, 1,25(OH)(2)D-3 regulates the expression of,its own receptors in C6 glioma. These results provide to our knowl edge the first evidence for a cytotoxic effect of 1,25(OH)(2)D-3 on ra t and human glioma cells and could offer both an experimental model to study a programmed cell death in a brain-derived cell line and a new strategy for the inhibition of glioma growth in vivo. (C) 1994 Wiley-L iss, Inc.