High basal NF-κB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-11-17

AUTHORS

Z Janjetovic, A A Brozyna, R C Tuckey, T-K Kim, M N Nguyen, W Jozwicki, S R Pfeffer, L M Pfeffer, A T Slominski

ABSTRACT

Background:Melanoma is highly resistant to current modalities of therapy, with the extent of pigmentation playing an important role in therapeutic resistance. Nuclear factor-κB (NF-κB) is constitutively activated in melanoma and can serve as a molecular target for cancer therapy and steroid/secosteroid action.Methods:Cultured melanoma cells were used for mechanistic studies on NF-κB activity, utilising immunofluorescence, western blotting, EMSA, ELISA, gene reporter, and estimated DNA synthesis assays. Formalin-fixed, paraffin-embedded specimens from melanoma patients were used for immunocytochemical analysis of NF-κB activity in situ.Results:Novel 20-hydroxyvitamin (20(OH)D3) and classical 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) secosteroids inhibited melanoma cell proliferation. Active forms of vitamin D were found to inhibit NF-κB activity in nonpigmented cells, while having no effect on pigmented cells. Treatment of nonpigmented cells with vitamin D3 derivatives inhibited NF-κB DNA binding and NF-κB-dependent reporter assays, as well as inhibited the nuclear translocation of the p65 NF-κB subunit and its accumulation in the cytoplasm. Moreover, analysis of biopsies of melanoma patients showed that nonpigmented and slightly pigmented melanomas displayed higher nuclear NF-κB p65 expression than highly pigmented melanomas.Conclusion:Classical 1,25(OH)2D3 and novel 20(OH)D3 hydroxyderivatives of vitamin D3 can target NF-κB and regulate melanoma progression in nonpigmented melanoma cells. Melanin pigmentation is associated with the resistance of melanomas to 20(OH)D3 and 1,25(OH)2D3 treatment. More... »

PAGES

1874-1884

References to SciGraph publications

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URI

http://scigraph.springernature.com/pub.10.1038/bjc.2011.458

DOI

http://dx.doi.org/10.1038/bjc.2011.458

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https://app.dimensions.ai/details/publication/pub.1025567432

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22095230


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