Influence of Tumor Suppressor p53 Functioning on the Expression of Antioxidant System Genes under the Action of Cytotoxic Compounds

Bull Exp Biol Med. 2020 May;169(1):169-175. doi: 10.1007/s10517-020-04844-3. Epub 2020 Jun 5.

Abstract

The effect of inhibition of the tumor suppressor p53 on the antioxidant system genes expression under the influence of cytotoxic compounds of the platinum group was studied. It was found that the action of platinum(II) and platinum(IV) complexes induced accumulation of p53 protein with a maximum in 12 h, which was confirmed by an increase in the expression of the P21 gene, the target gene of the p53 protein. It was shown that the action of platinum complexes activated the expression of catalase and superoxide dismutase 2 genes. Suppression of p53 protein functions with specific inhibitor α-piphitrin under the action of platinum complexes reduced the expression of catalase and superoxide dismutase 2 genes and the target gene P21, which attested to the p53-dependent regulation of these genes.

Keywords: antioxidant system; gene expression of the antioxidant system; p53 tumor suppressor; platinum complexes; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Catalase / drug effects
  • Catalase / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • DNA Repair Enzymes / genetics
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Cyclin-Dependent Kinase Inhibitor p21
  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Catalase
  • Superoxide Dismutase
  • superoxide dismutase 2
  • DNA Repair Enzymes