Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Bone Cancer

Thomas S Lisse

doi:10.3390/app10072554

Abstract

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. First, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10 nM but not at 100 nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 h of 10 nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 ours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

Highlights

Vitamin D is a steroid hormone produced in the skin, or obtained in varying quantities through dietary or supplementary means [1]
The switch from superoxide dismutase 1 (SOD1) to SOD2 may signify the importance of the cellular distribution and actions of each superoxide dismutase (SOD) enzyme, cytosol versus mitochondria, respectively. These findings suggest an active time- and concentration-dependent mitochondrial reparative process involving specific SOD enzymes engaged after vitamin D treatment within MG-63 osteosarcoma cells as part of vitamin
D has non-calcemic functions in controlling the cell cycle, differentiation and apoptosis,that and its analogues are used in cancer treatment

Summary

Introduction

Vitamin D is a steroid hormone produced in the skin, or obtained in varying quantities through dietary or supplementary means [1]. Vitamin D is metabolized through two subsequent hydroxylation steps that occur in the liver and kidney, resulting in its metabolically active form, 1,25(OH) D3 ( known as calcitriol or 1,25D3 ). Calcitriol is synthesized from its precursor in the kidney but as well as in certain tissues including bone, prostate and breast through expression of its hydroxylases, to maintain local non-endocrine-mediated cellular responses [17]. Vitamin D is essential for proper bone health [17]. Vitamin D deficiency causes metabolic bone diseases like osteomalacia and can exacerbate osteoporosis [17]. Vitamin D and certain analogues can regulate growth and differentiation among human and murine bone cells within in vitro culture systems [18,19]. Vitamin D has anabolic effects to stimulate and10,bone precursor

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