Protective activity of a novel resveratrol analogue, HS-1793, against DNA damage in 137Cs-irradiated CHO-K1 cells

J Radiat Res. 2014 May;55(3):464-75. doi: 10.1093/jrr/rrt140. Epub 2014 Jan 7.

Abstract

Resveratrol has received considerable attention as a polyphenol with anti-oxidant, anti-carcinogenic, and anti-inflammatory effects. Radiation is an important component of therapy for a wide range of malignant conditions. However, it causes damage to normal cells and, hence, can result in adverse side effects. This study was conducted to examine whether HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, induces a protective effect against radiation-induced DNA damage. HS-1793 effectively scavenged free radicals and inhibited radiation-induced plasmid DNA strand breaks in an in vitro assay. HS-1793 significantly decreased reactive oxygen species and cellular DNA damage in 2 Gy-irradiated Chinese hamster ovary (CHO)-K1 cells. In addition, HS-1793 dose-dependently reduced the levels of phosphorylated H2AX in irradiated CHO-K1 cells. These results indicate that HS-1793 has chemical radioprotective activity. Glutathione levels and superoxide dismutase activity in irradiated CHO-K1 cells increased significantly following HS-1793 treatment. The enhanced biological anti-oxidant activity and chemical radioprotective activity of HS-1793 maintained survival of irradiated CHO-K1 cells in a clonogenic assay. Therefore, HS-1793 may be of value as a radioprotector to protect healthy tissue surrounding tumor cells during radiotherapy to obtain better tumor control with a higher dose.

Keywords: DNA strand break; HS-1793; free radical scavenging activity; radioprotection; reactive oxygen species (ROS); resveratrol analogue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Survival / drug effects
  • Cell Survival / genetics*
  • Cell Survival / radiation effects*
  • Cesium Radioisotopes / pharmacology*
  • Cricetinae
  • Cricetulus
  • DNA Damage / drug effects*
  • DNA Damage / genetics*
  • Dose-Response Relationship, Drug
  • Naphthols / administration & dosage*
  • Radiation Dosage
  • Radiation Tolerance / drug effects
  • Radiation Tolerance / physiology*
  • Radiation-Protective Agents / administration & dosage
  • Resorcinols / administration & dosage*

Substances

  • 4-(6-hydroxy-2-naphthyl)-1,3-benzenediol
  • Cesium Radioisotopes
  • Naphthols
  • Radiation-Protective Agents
  • Resorcinols