Radioprotective effects of genistein on HL-7702 cells via the inhibition of apoptosis and DNA damage

Cancer Lett. 2015 Sep 28;366(1):100-11. doi: 10.1016/j.canlet.2015.06.008. Epub 2015 Jun 18.

Abstract

Radiation induced normal tissue damage is the most important limitation for the delivery of a high potentially curative radiation dose. Genistein (GEN), one of the main soy isoflavone components, has drawn wide attention for its bioactivity in alleviating radiation damage. However, the effects and molecular mechanisms underlying the radioprotective effects of GEN remain unclear. In the present study, we showed that low concentration of GEN (1.5 µM) protected L-02 cells against radiation damage via inhibition of apoptosis, alleviation of DNA damage and chromosome aberration, down-regulation of GRP78 and up-regulation of HERP, HUS1 and hHR23A. In contrast, high concentration of GEN (20 µM) demonstrated radiosensitizing characteristics through the promotion of apoptosis and chromosome aberration, impairment of DNA repair, up-regulation of GRP78, and down-regulation of HUS1, SIRT1, RAD17, RAD51 and RNF8. These findings shed light on using low, but not high-concentration GEN, as a potential candidate for adjuvant therapy to alleviate radiation-induced injuries to human recipients of ionizing radiation.

Keywords: Apoptosis; Chromosome aberrations; DNA damage; Genistein; Radioprotective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chromosome Aberrations
  • DNA Damage*
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / genetics
  • Dose-Response Relationship, Radiation
  • Endoplasmic Reticulum Chaperone BiP
  • Genistein / pharmacology*
  • Heat-Shock Proteins / genetics
  • Humans
  • Membrane Proteins / genetics
  • Radiation-Protective Agents / pharmacology*
  • X-Rays

Substances

  • DNA-Binding Proteins
  • Endoplasmic Reticulum Chaperone BiP
  • HERPUD1 protein, human
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Membrane Proteins
  • Radiation-Protective Agents
  • RAD23A protein, human
  • Genistein
  • DNA Repair Enzymes