1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(
OH)2D3) has recently been reported to exert a toxic effect on both rat and human
glioma cell lines. However the potential clinical use of 1 alpha,25(
OH)2D3 in the treatment of
glioma is impaired by its potent hypercalcemic effects. We have therefore investigated the effects on
glioma cell growth of several
vitamin D3 analogues which have previously been shown to be less calcemic in vivo than 1 alpha,25(
OH)2D3. The present study shows that several analogues are able to induce, in vitro, the death of rat
glioma cells (C6.9). The compound
KH 1060 appears to be the most effective in the induction of cell death, while
MC 1288 and
CB 1093 are as potent as 1 alpha,25(
OH)2D3.
EB 1089 was somewhat less effective than 1 alpha,25(
OH)2D3 and
MC 903, which is currently used in the treatment of
psoriasis, has only a weak activity on C6.9 cells. The effective doses used are around 10(-9) M for 1 alpha,25(
OH)2D3 and 10(-10) M for
KH 1060. Interestingly, the toxic effect exerted by 1 alpha,25(
OH)2D3 and its analogues is accompanied by several of the biochemical features of apoptosis, such as DNA fragmentation and induction of the c-myc protooncogene. These findings, together with the fact that the
therapies currently available for
glioma are only palliative, suggest that 1 alpha,25(
OH)2D3 analogues such as
KH 1060,
EB 1089 or
CB 1093, alone or in combination with other therapeutic approaches, could be of potential interest in the treatment of brain glial
tumors.