The Effect of Cannabidiol on UV-Induced Changes in Intracellular Signaling of 3D-Cultured Skin Keratinocytes

Int J Mol Sci. 2021 Feb 2;22(3):1501. doi: 10.3390/ijms22031501.

Abstract

Human epidermal keratinocytes are constantly exposed to UV radiation. As a result, there is a significant need for safe and effective compounds to protect skin cells against this environmental damage. This study aimed to analyze the effect of phytocannabinoid-cannabinoid (CBD)-on the proteome of UVA/B irradiated keratinocytes. The keratinocytes were cultured in a three-dimensional (3D) system, designed to mimic epidermal conditions closely. The obtained results indicate that CBD protected against the harmful effects of UVA/B radiation. CBD decreased the expression of proinflammatory proteins, including TNFα/NFκB and IκBKB complex and decreased the expression of proteins involved in de novo protein biosynthesis, which are increased in UVA/B-irradiated cells. Additionally, CBD enhanced the UV-induced expression of 20S proteasome subunits. CBD also protected protein structures from 4-hydroxynonenal (HNE)-binding induced by UV radiation, which primarily affects antioxidant enzymes. CBD-through its antioxidant/anti-inflammatory activity and regulation of protein biosynthesis and degradation-protects skin cells against UVA/B-induced changes. In the future, its long-term use in epidermal cells should be investigated.

Keywords: UV irradiated skin; cannabidiol; keratinocytes; lipid peroxidation products adducts formation; proteomics; three-dimensional in vitro culture.

MeSH terms

  • Aldehydes / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Cannabidiol / chemistry
  • Cannabidiol / pharmacology*
  • Cell Culture Techniques
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Humans
  • I-kappa B Kinase / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • Molecular Structure
  • Multiprotein Complexes / metabolism
  • NF-kappa B / metabolism
  • Principal Component Analysis
  • Proteome / drug effects*
  • Proteome / radiation effects
  • Signal Transduction / drug effects*
  • Signal Transduction / radiation effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultraviolet Rays*

Substances

  • Aldehydes
  • Anti-Inflammatory Agents
  • Antioxidants
  • Multiprotein Complexes
  • NF-kappa B
  • Proteome
  • Tumor Necrosis Factor-alpha
  • Cannabidiol
  • I-kappa B Kinase
  • 4-hydroxy-2-nonenal