1,25-DihydroxyVitamin D(3) and analogs have been shown to inhibit proliferation and to induce differentiation in different cell types, including human melanocytes. However, various tumor cell lines that fail to respond to the antiproliferative effects of
Vitamin D analogs have also been reported. Using real-time PCR (LightCycler), we have compared
mRNA expression of
Vitamin D receptor (VDR),
Vitamin D-25-hydroxylase (25-OHase), 25-hydroxyVitamin D-1alpha-hydroxylase (1alpha-OHase), and 1,25-dihydroxyVitamin D-24-hydroxylase (24-OHase) in a
melanoma cell line that responds to antiproliferative effects of
Vitamin D (MeWo) with a non-responsive
melanoma cell line (SkMel5). Additionally, modulation of cell proliferation by
calpain inhibitors, as well as regulation of
mRNA expression of VDR, 1alpha-OHase, and 24-OHase genes by
Vitamin D analogs were assessed in
melanoma cell lines in vitro using a WST-1 based colorimetric assay and real-time PCR, respectively.
RNA for VDR, 25-OHase, 1alpha-OHase, and 24-OHase was detected in
melanoma cell lines. In contrast to SkMel5 cells, treatment of MeWo cells with
calcitriol resulted in a dose-dependent increase in
mRNA for VDR and 24-OHase as well as in a suppression of cell proliferation (up to approximately 50%). Our findings demonstrate that local synthesis or metabolism of
Vitamin D metabolites may be of importance for growth regulation of MM and
melanoma cell lines. Additionally, metastasizing MM represents a promising target for
palliative treatment with new
Vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of
calcitriol synthesis/metabolism in these
tumors.