title: Evaluation of cytotoxic effects of 7-dehydrocholesterol on melanoma cells.
abstract: Ultraviolet radiation is the main cause of skin cancers, and melanoma is the most serious form of tumor. There is no therapy for advanced-stage melanoma and its metastasis because of their high resistance to various anticancer therapies. Human skin is an important metabolic organ in which occurs photoinduced synthesis of vitamin D3 from 7-dehydrocholesterol (7-DHC). 7-DHC, the precursor of cholesterol biosynthesis, is highly reactive and easily modifiable to produce 7-DHC-derived compounds. The intracellular levels of 7-DHC or its derivatives can have deleterious effects on cellular functionality and viability. In this study we evaluated the effects on melanoma cell lines of 7-DHC as such and for this aim we used much care to minimize 7-DHC modifications. We found that from 12 to 72 h of treatment 82-86% of 7-DHC entered the cells, and the levels of 7-DHC-derived compounds were not significant. Simultaneously, reactive oxygen species production was significantly increased already after 2h. After 24 h and up to 72 h, 7-DHC-treated melanoma cells showed a reduction in cell growth and viability. The cytotoxic effect of 7-DHC was associated with an increase in Bax levels, decrease in Bcl-2/Bax ratio, reduction of mitochondrial membrane potential, increase in apoptosis-inducing factor levels, unchanged caspase-3 activity, and absence of cleavage of PARP-1. These findings could explain the mechanism through which 7-DHC exerts its cytotoxic effects. This is the first report in which the biological effects found in melanoma cells are mainly attributable to 7-DHC as such.
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche and.
authors.forename: Monica
authors.initials: M
authors.lastname: Gelzo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche and.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Granato
authors.affiliation: Dipartimento di Sanità Pubblica, Università degli Studi di Napoli Federico II, I-80131 Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Albano
authors.affiliation: Dipartimento di Sanità Pubblica, Università degli Studi di Napoli Federico II, I-80131 Napoli, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Arcucci
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Dello Russo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche and.
authors.forename: Emmanuele
authors.initials: E
authors.lastname: De Vendittis
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche and. Electronic address: ruocco@dbbm.unina.it.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ruocco
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Foggia, I-71122 Foggia, Italy. Electronic address: gaetano.corso@unifg.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Corso
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D003684:Dehydrocholesterols / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D009367:Neoplasm Staging; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D003684:Dehydrocholesterols; C016705:7-dehydrocholesterol
keywords: 7-Dehydrocholesterol; Apoptosis; Free radicals; Melanoma cells; Mitochondrial membrane potential; Radical oxygen species