Noncalcemic Vitamin D hydroxyderivatives inhibit human oral squamous cell carcinoma and down-regulate hedgehog and WNT/β-catenin pathways

Academic Article

Abstract

  • Background/Aim: The hormonally-active form of Vitamin D, 1,25(OH)2D3, demonstrated activity against oral squamous cell carcinoma (OSCC). Cytochrome P450scc (CYP11A1)-derived Vitamin D hydroxyderivatives, such as 20(OH)D3 and 1,20(OH)2D3, have overlapping beneficial effects with 1,25(OH)2D3 without causing hypercalcemia. This study sought to determine (i) whether 20(OH)D3 and 1,20(OH)2D3 exhibit antitumor effects against OSCC comparable to those of 1,25(OH)2D3 and (ii) whether these effects may stem from down-regulation of sonic hedgehog (SHH) or WNT/β-catenin signaling pathways. Materials and Methods: Effects on CAL-27 cells were assessed by 3-(4,5- dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium inner salt and spheroid assays. Signaling pathways were assessed by immunofluorescence and western blotting. Results: 20(OH)D3 and 1,20(OH)2D3 inhibited the growth of CAL-27 and demonstrated inhibition of WNT/β-catenin and the SHH signaling as evidenced by down-regulation of nuclear translocation of glioma-associated oncogene 1(GLI1) and β-catenin. Conclusion: Noncalcemic Vitamin D hydroxyderivatives demonstrated antitumor activities against OSCC comparable to those of 1,25(OH)2D3. Their activities against SHH and the WNT/β-catenin pathways provide insight for a possible target for OSCC treatment.
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    Author List

  • Oak ASW; Bocheva G; Kim TK; Brozyna AA; Janjetovic Z; Athar M; Tuckey RC; Slominski AT
  • Start Page

  • 2467
  • End Page

  • 2474
  • Volume

  • 40
  • Issue

  • 5