Antitumor effects of vitamin D analogs on hamster and mouse melanoma cell lines in relation to melanin pigmentation.

Abstract

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)2D3) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)2D3 and 25(OH)D3), and novel relatively non-calcemic ones (20(OH)D3, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OH)pL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.

• Authors: Tomasz Wasiewicz, Paulina Szyszka, Miroslawa Cichorek, Zorica Janjetovic, Robert C Tuckey, Andrzej T Slominski, Michal A Zmijewski
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 16 Issue 4 Pg. 6645-67 (Mar 24 2015) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 25811927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Melanins
• Receptors, Calcitriol
• VDR protein, human
• Vitamin D
• calcipotriene
• CYP24A1 protein, human
• Vitamin D3 24-Hydroxylase
• Calcitriol

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Calcitriol (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cricetinae
• Gene Expression Regulation, Neoplastic (drug effects)
• Melanins (metabolism)
• Melanoma (drug therapy, pathology)
• Mice
• Receptors, Calcitriol (genetics)
• Signal Transduction (drug effects)
• Skin Neoplasms (drug therapy, metabolism)
• Vitamin D (analogs & derivatives)
• Vitamin D3 24-Hydroxylase (genetics)