title: 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: Department of Histology, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland. tomwasxp@poczta.onet.pl.
authors: Tomasz
authors: T
authors: Wasiewicz
authors: Department of Histology, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland. pszyszka@gumed.edu.pl.|Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland. pszyszka@gumed.edu.pl.
authors: Paulina
authors: P
authors: Szyszka
authors: Department of Embryology, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland. cichorek@gumed.edu.pl.
authors: Miroslawa
authors: M
authors: Cichorek
authors: Department of Dermatology, University of Alabama Birmingham, VA Medical Center, Birmingham, AL 35294, USA. zjanjeto@uthsc.edu.
authors: Zorica
authors: Z
authors: Janjetovic
authors: School of Chemistry and Biochemistry, the University of Western Australia, Crawley, Perth, WA 6009, Australia. robert.tuckey@uwa.edu.au.
authors: Robert C
authors: RC
authors: Tuckey
authors: Department of Dermatology, University of Alabama Birmingham, VA Medical Center, Birmingham, AL 35294, USA. aslomins@uthsc.edu.
authors: Andrzej T
authors: AT
authors: Slominski
authors: Department of Histology, Medical University of Gdańsk, Dębinki 1a, 80-211 Gdańsk, Poland. mzmijewski@gumed.edu.pl.
authors: Michal A
authors: MA
authors: Zmijewski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018167:Receptors, Calcitriol / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D008543:Melanins; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C055085:calcipotriene; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol