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

T. Wasiewicz, P. Szyszka, M. Cichorek, Z. Janjetovic, Robert Tuckey, A.T. Słomiński, M.A. Zmijewski

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

© 2015 by the authors; licensee MDPI, Basel, Switzerland. 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.
Original languageEnglish
Pages (from-to)6645-6667
JournalInternational Journal of Molecular Sciences
Volume16
Issue number4
DOIs
Publication statusPublished - 2015

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calciferol
Melanin
melanin
hamsters
Vitamins
Melanins
Pigmentation
cultured cells
Vitamin D
Cricetinae
mice
Melanoma
Cells
analogs
Cell Line
rodents
Rodentia
genes
Genes
Ligands

Cite this

Wasiewicz, T. ; Szyszka, P. ; Cichorek, M. ; Janjetovic, Z. ; Tuckey, Robert ; Słomiński, A.T. ; Zmijewski, M.A. / Antitumor effects of vitamin D analogs on hamster and mouse melanoma cell lines in relation to melanin pigmentation. In: International Journal of Molecular Sciences. 2015 ; Vol. 16, No. 4. pp. 6645-6667.
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Antitumor effects of vitamin D analogs on hamster and mouse melanoma cell lines in relation to melanin pigmentation. / Wasiewicz, T.; Szyszka, P.; Cichorek, M.; Janjetovic, Z.; Tuckey, Robert; Słomiński, A.T.; Zmijewski, M.A.

In: International Journal of Molecular Sciences, Vol. 16, No. 4, 2015, p. 6645-6667.

Research output: Contribution to journalArticle

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T1 - Antitumor effects of vitamin D analogs on hamster and mouse melanoma cell lines in relation to melanin pigmentation

AU - Wasiewicz, T.

AU - Szyszka, P.

AU - Cichorek, M.

AU - Janjetovic, Z.

AU - Tuckey, Robert

AU - Słomiński, A.T.

AU - Zmijewski, M.A.

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N2 - © 2015 by the authors; licensee MDPI, Basel, Switzerland. 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.

AB - © 2015 by the authors; licensee MDPI, Basel, Switzerland. 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.

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