Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

International Journal of Molecular Sciences

Tomasz Wasiewicz²  Paulina Szyszka²  Miroslawa Cichorek³  Zorica Janjetovic¹  Robert C. Tuckey⁴  Andrzej T. Slominski¹ 

[1] Department of Dermatology, University of Alabama Birmingham, VA Medical Center, Birmingham, AL 35294, USA; E-Mails:;Department of Histology, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland; E-Mails:;Department of Embryology, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland; E-Mail:;School of Chemistry and Biochemistry, the University of Western Australia, Crawley, Perth, WA 6009, Australia; E-Mail:

关键词: vitamin D;    1;    25(OH)₂D₃;    vitamin D analogs;    secosteroids;    lumisterol melanoma;    melanin pigmentation;    anti-melanoma effect;   

DOI  :  10.3390/ijms16046645

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.