Evaluation of cytotoxic effects of 7-dehydrocholesterol on melanoma cells

Monica Gelzo, Giuseppina Granato, Francesco Albano, Alessandro Arcucci, Antonio Dello Russo, Emmanuele De Vendittis, Maria Rosaria Ruocco, Gaetano Corso

Research output: Contribution to journalArticle

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 2 h. 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.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalFree Radical Biology and Medicine
Volume70
DOIs
Publication statusPublished - 2014

Keywords

  • 7-Dehydrocholesterol
  • Apoptosis
  • Free radicals
  • Melanoma cells
  • Mitochondrial membrane potential
  • Radical oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

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  • Cite this

    Gelzo, M., Granato, G., Albano, F., Arcucci, A., Dello Russo, A., De Vendittis, E., Ruocco, M. R., & Corso, G. (2014). Evaluation of cytotoxic effects of 7-dehydrocholesterol on melanoma cells. Free Radical Biology and Medicine, 70, 129-140. https://doi.org/10.1016/j.freeradbiomed.2014.02.013