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

Z Janjetovic1, A A Brozyna, R C Tuckey

  • 1Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN 38163, USA.

British Journal of Cancer
|November 19, 2011
PubMed
Abstract

Insights

Vitamin D derivatives inhibit melanoma cell growth by targeting Nuclear Factor-kappa B (NF-κB) in nonpigmented cells. However, melanin pigmentation in melanoma cells causes resistance to these vitamin D treatments.

Area of Science:

  • Oncology
  • Dermatology
  • Endocrinology

Background:

  • Melanoma exhibits significant resistance to conventional therapies.
  • Melanin pigmentation plays a crucial role in melanoma's therapeutic resistance.
  • Nuclear Factor-kappa B (NF-κB) is constitutively active in melanoma and represents a potential therapeutic target.

Purpose of the Study:

  • To investigate the effects of vitamin D secosteroids on melanoma cell proliferation and NF-κB activity.
  • To determine the role of pigmentation in melanoma's response to vitamin D therapy.

Main Methods:

  • Mechanistic studies using cultured melanoma cells (immunofluorescence, western blotting, EMSA, ELISA, gene reporter, DNA synthesis assays).
  • In situ analysis of NF-κB activity in patient melanoma specimens using immunocytochemistry.

Main Results:

  • Both 20-hydroxyvitamin D3 (20(OH)D3) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibited melanoma cell proliferation.
  • Vitamin D inhibited NF-κB activity in nonpigmented melanoma cells but not in pigmented cells.
  • Patient data revealed higher NF-κB p65 expression in less pigmented melanomas.

Conclusions:

  • Vitamin D3 derivatives (1,25(OH)2D3 and 20(OH)D3) can target NF-κB and modulate melanoma progression in nonpigmented cells.
  • Melanin pigmentation confers resistance to these vitamin D treatments in melanoma.

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