title: Antiproliferative Effects of 1α-OH-vitD3in Malignant Melanoma: Potential Therapeutic implications.
abstract: Early detection and surgery represent the mainstay of treatment for superficial melanoma, but for high risk lesions (Breslow's thickness >0.75 mm) an effective adjuvant therapy is lacking. Vitamin D insufficiency plays a relevant role in cancer biology. The biological effects of 1α hydroxycholecalciferol on experimental melanoma models were investigated. 105 melanoma patients were checked for 25-hydroxycholecalciferol (circulating vitamin D) serum levels. Human derived melanoma cell lines and in vivo xenografts were used for studying 1α-hydroxycholecalciferol-mediated biological effects on cell proliferation and tumor growth. 99 out of 105 (94%) melanoma patients had insufficient 25-hydroxycholecalciferol serum levels. Interestingly among the six with vitamin D in the normal range, five had a diagnosis of in situ/microinvasive melanoma. Treatment with 1α-hydroxycholecalciferol induced antiproliferative effects on melanoma cells in vitro and in vivo, modulating the expression of cell cycle key regulatory molecules. Cell cycle arrest in G1 or G2 phase was invariably observed in vitamin D treated melanoma cells. The antiproliferative activity induced by 1α-hydroxycholecalciferol in experimental melanoma models, together with the discovery of insufficient 25-hydroxycholecalciferol serum levels in melanoma patients, provide the rationale for using vitamin D in melanoma adjuvant therapy, alone or in association with other therapeutic options.
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Spath
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.|Laboratory of Biomedical Research, Niccolò Cusano University Foundation, via Don Carlo Gnocchi 3, 00166 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ulivieri
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.|Laboratory of Biomedical Research, Niccolò Cusano University Foundation, via Don Carlo Gnocchi 3, 00166 Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Lavra
authors.affiliation: Dermatology Unit, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fidanza
authors.affiliation: Dermatology Unit, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Carlesimo
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Giubettini
authors.affiliation: Dermatology Unit, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Narcisi
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Emidio
authors.initials: E
authors.lastname: Luciani
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bucci
authors.affiliation: Internal Medicine Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pisani
authors.affiliation: Laboratory of Biomedical Research, Niccolò Cusano University Foundation, via Don Carlo Gnocchi 3, 00166 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sciacchitano
authors.affiliation: Pathology Research Laboratory, Sant'Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy.|Molecular and Cellular Tumor Pathology Laboratory, Cancer Center Karolinska, Karolinska Hospital, CCK R8:04, S-17176, Stockholm, Sweden.
authors.forename: Armando
authors.initials: A
authors.lastname: Bartolazzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged
chemical_list: D004872:Ergocalciferols; D006887:Hydroxycholecalciferols; C084656:paricalcitol; C008088:alfacalcidol