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. 2020 Mar 5;25(5):1164.
doi: 10.3390/molecules25051164.

Beneficial Regulation of Cellular Oxidative Stress Effects, and Expression of Inflammatory, Angiogenic, and the Extracellular Matrix Remodeling Proteins by 1α,25-Dihydroxyvitamin D3 in a Melanoma Cell Line

Neena Philips  1 , Philips Samuel  2 , Thomas Keller  2 , Asma Alharbi  2 , Samar Alshalan  2 , Sara-Ali Shamlan  2
Affiliations

Beneficial Regulation of Cellular Oxidative Stress Effects, and Expression of Inflammatory, Angiogenic, and the Extracellular Matrix Remodeling Proteins by 1α,25-Dihydroxyvitamin D3 in a Melanoma Cell Line

Neena Philips et al. Molecules. .

Abstract

The causes of cancer include the cellular accumulation reactive oxygen species (ROS), which overrides the cellular antioxidants such as superoxide dismutase, from intrinsic aging, genetics, and exposure to environmental pollutants and ultraviolet (UV) radiation. The ROS damage biomolecules such as DNA (including p53 gene), RNA, and lipids, and activate inflammatory, angiogenic, and extracellular matrix (ECM) remodeling proteins; which collectively facilitate carcinogenesis. The 1α,25-dihydroxyvitamin D3 (Vitamin D) has anti-carcinogenic potential from its antioxidant, anti-inflammatory, and endocrine properties. We examined the anti-carcinogenic mechanism of vitamin D through the beneficial regulation of oxidative stress effects (oxidative DNA/RNA damage, superoxide dismutase expression, membrane damage, and p53 promoter activity), and expression (at the protein, mRNA and/or promoter levels) of inflammatory mediators (interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α)), angiogenic mediators (transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF)), and the ECM remodeling proteins (matrix metalloproteinases (MMP)-1 and MMP-2) by vitamin D in melanoma cells. Vitamin D inhibited oxidative DNA/RNA damage and membrane damage; and stimulated superoxide dismutase expression and p53 promoter activity in melanoma cells. It inhibited the expression of IL-1, TNF-α, TGF-β, VEGF, MMP-1 and MMP-2 by transcriptional or post-transcriptional mechanisms. We conclude that vitamin D is beneficial to melanoma cells through the inhibition of oxidative DNA/RNA damage, membrane damage, and the expression of inflammatory, angiogenic and ECM remodeling proteins; and the stimulation of superoxide dismutase expression and p53 promoter activity.

Keywords: interleukin-1; matrix metalloproteinases; oxidative DNA/RNA damage; p53; superoxide dismutase; transforming growth factor-β; tumor necrosis factor-α; vascular endothelial growth factor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of 1α,25-dihydroxyvitamin D3 (vitamin D) on 8-OH-dGuanine/8-OH-Guanine (oxidative DNA/RNA damage) (A), and superoxide dismutase protein levels (B) in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 2
Figure 2
Effect of 1α,25-dihydroxyvitamin D3 (vitamin D) on p53 promoter activity (A), and lactate dehydrogenase activity (membrane damage) (B) in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 3
Figure 3
Effect of 1α,25-dihydroxyvitamin D3 (vitamin D) on interleukin-1 (IL-1) (A), and tumor necrosis factor alpha (TNF-α) (B) protein levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 4
Figure 4
Effect of 0.02 µM 1α,25-dihydroxyvitamin D3 (vitamin D) on interleukin-1 (IL-1) (A), and tumor necrosis factor alpha (TNF-α) (B) mRNA levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 4
Figure 4
Effect of 0.02 µM 1α,25-dihydroxyvitamin D3 (vitamin D) on interleukin-1 (IL-1) (A), and tumor necrosis factor alpha (TNF-α) (B) mRNA levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 5
Figure 5
Effect of 1α,25-dihydroxyvitamin D3 (vitamin D) on transforming growth factor beta (TGF-β) (A), and vascular endothelial growth factor (VEGF) (B) protein levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 5
Figure 5
Effect of 1α,25-dihydroxyvitamin D3 (vitamin D) on transforming growth factor beta (TGF-β) (A), and vascular endothelial growth factor (VEGF) (B) protein levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 6
Figure 6
Effect of 0.02 µM 1α,25-dihydroxyvitamin D3 (vitamin D) on transforming growth factor beta (TGF-β) (A), and vascular endothelial growth factor (VEGF) (B) mRNA levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
Figure 7
Figure 7
Effect of 1α,25-dihydroxyvitamin D3 (vitamin D) on Matrix metalloproteinase (MMP)-1 (A), and MMP-2 (B) protein levels in melanoma cells; error bars: standard deviation, n = 4; * = p < 0.05, relative to control.
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