We studied effects of
1,25-dihydroxyvitamin D3 [
1,25(OH)2D3], its analog
seocalcitol (
EB 1089), and
25-hydroxyvitamin D3 [25(
OH)D3], on the growth of seven
melanoma cell lines. While three cell lines (MeWo, SK-Mel-28, SM) responded to antiproliferative effects of active
vitamin D analogs, the others (SK-Mel-5, SK-Mel-25, IGR, MeUuso) were resistant. A strong induction (7000-fold) of 1,25-dihydroxyvitamin D-24-hydroxylase (24OHase, CYP24)
mRNA was detected in responsive cell lines along with 1,25(OH)2D3-treatment, indicating functional integrity of
vitamin D receptor (VDR)-mediated transcription. In contrast, induction of 24OHase was much lower in resistant
melanoma cells (70-fold). VDR
mRNA was induced up to 3-fold both in responsive and resistant cell lines along with 1,25(OH)2D3-treatment.
RNA for
vitamin D-activating
enzymes vitamin D-25-hydroxylase (25OHase, CYP27A1) and
25-hydroxyvitamin D-lalpha-
hydroxylase (lalphaOHase,
CYP27B1) was detected in all
melanoma cell lines analyzed, additionally we show splicing variants of lalphaOHase in SK-Mel-28 cells. Expression of 250Hase and laOHase was marginally modulated along with treatment. Proliferation of
melanoma cells was not inhibited by treatment with 25(
OH)D3, indicating no significant stimulation of endogeneous production of antiproliferative acting
1,25(OH)2D3. In conclusion, we characterize the
vitamin D endocrine system in
melanoma cells and demonstrate that the majority of
melanoma cell lines analyzed is resistant to antiproliferative effects of
1,25(OH)2D3. It can be speculated that these alterations are of importance for pathogenesis and growth of metastasizing
malignant melanoma. Additionally, our findings indicate that only a minority of cases with metastasizing
melanoma may represent a promising target for
palliative treatment with new
vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of
1,25(OH)2D3-synthesis/metabolism.