title: Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes.
abstract: OBJECTIVE
  To test the activity of novel hydroxyvitamin D(3) analogs (20(OH)D(3), 20,23(OH)(2)D and 1,20(OH)(2)D(3)) on normal and malignant melanocytes in comparison to 1,25(OH)(2)D(3).
  
  
  METHODS
  Human epidermal melanocytes and human and hamster melanoma cells were used to measure effects on proliferation and colony formation in monolayer and soft agar. Cell morphology and melanogenesis were also analyzed. QPCR was used to measure gene expression.
  
  
  RESULTS
  Novel secosteroids inhibited proliferation and colony formation by melanoma cells in a similar fashion to 1,25(OH)(2)D(3), having no effect on melanogenesis. These effects were accompanied by ligand-induced translocation of VDR to the nucleus. In normal melanocytes 1α-hydroxyderivatives (1,25(OH)(2)D(3) and 1,20(OH)(2)D(3)) had stronger anti-proliferative effects than 20(OH)D(3) and 20,23(OH)(2)D(3), and inhibited dendrite formation. The cells tested expressed genes encoding VDR and enzymes that activate or inactivate vitamin D(3).
  
  
  CONCLUSIONS
  Novel secosteroids show potent anti-melanoma activity in vitro with 20(OH)D(3) and 20,23(OH)(2)D(3) being excellent candidates for pre-clinical testing.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. aslominski@uthsc.edu
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.forename: Zorica
authors.initials: Z
authors.lastname: Janjetovic
authors.forename: Tae-Kang
authors.initials: TK
authors.lastname: Kim
authors.forename: Adam C
authors.initials: AC
authors.lastname: Wright
authors.forename: Laura N
authors.initials: LN
authors.lastname: Grese
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Riney
authors.forename: Minh N
authors.initials: MN
authors.lastname: Nguyen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tuckey
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006224:Cricetinae; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D014815:Vitamins; D002117:Calcitriol