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 major biologically active metabolite of vitamin D. Antitumor activity of this hormone has been observed on several cell lines and on breast cancer in vivo. The purpose of this in vitro study was to determine the possible 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 assessed 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 observation 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 challenged for 24 hr with 1,25(OH)(2)D-3 and then cultured in the absence 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 knowledge the first evidence for a cytotoxic effect of 1,25(OH)(2)D-3 on rat 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-Liss, Inc.