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Trends in Cancer Research   Volumes    Volume 18 
Regulation of cell proliferation, lipid peroxidation, and the expression of p53, NF-kB, interleukin-1, vascular endothelial growth factor, transforming growth factor-β, elastase, matrix metalloproteinase-1 and heat shock protein-90 in melanoma cells by copper
Neena Philips, Nadyeh Almeshni, David Bynum, Giselle Perez, Susan Auler, Jonathan Pena, Asher Richardson, Marcel Paradise, Purnima Sengupta
Pages: 21 - 27
Number of pages: 7
Trends in Cancer Research
Volume 18 

Copyright © 2023 Research Trends. All rights reserved

Carcinogenesis is associated with cell proliferation and metastasis, facilitated by oxidative stress, inflammation, angiogenesis and remodeling of the extracellular matrix (ECM) proteins. Cancer cell proliferation is supported by reduced expression of p53. Oxidative stress is associated with increased expression of heat shock proteins (HSP) and oxidative damage to the biomolecules, including membrane lipids. Inflammation and angiogenesis are associated with increased levels of NF-kB, interleukin-1 (IL-1), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGF-β). ECM remodeling is associated with increased levels of elastase and matrix metalloproteinases (MMP). Copper is an environmental pollutant. It has skin modulating and wound healing properties. We previously reported the stimulation of cell proliferation and the expression of VEGF, TGF-β and MMP-1, and inhibition of lipid peroxidation and membrane damage, by copper in dermal fibroblasts. While these alterations would support anti-skin aging and wound healing, these could support carcinogenesis by copper. This research investigated copper’s effects on melanoma cells. Copper stimulated cell proliferation and inhibited p53 promoter activity in melanoma cells. It stimulated the expression of NF-kB, IL-1, VEGF, TGF-β, elastase and MMP-1, and inhibited heat shock protein-90 and lipid peroxidation in melanoma cells, similar to copper’s effects on fibroblast cells. We infer that copper can support melanoma cell growth and metastasis, through the inhibition of p53 promoter activity, and the stimulation of the examined inflammatory, angiogenesis, and ECM remodeling mediators, and these effects are by mechanisms other than oxidative stress.
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