Activating AKT to inhibit JNK by troxerutin antagonizes radiation-induced PTEN activation

Eur J Pharmacol. 2017 Jan 15:795:66-74. doi: 10.1016/j.ejphar.2016.11.052. Epub 2016 Dec 2.

Abstract

Radiotherapy is one of the most effective non-surgical treatments for many tumors. However, radiation damage remains a major negative consequence of radiotherapy. At present, radio-protective effect of troxerutin has been confirmed, but the mechanism of this radioprotection has not been elucidated. Here, this study showed that troxerutin protected thymus tissue of irradiated mice, and its radio-protective effect on thymocytes was significant in the range of 0.625-10μg/ml. Troxerutin significantly inhibited apoptosis of irradiated thymocytes at the concentration of 10μg/ml. Computer-aided drug design was used to investigate potential candidate targets for troxerutin, and an excellent correlation was identified between troxerutin and AKT (Pharm mapper and KEGG signal pathway). Troxerutin inhibited the activation of PTEN to stimulate AKT, which in turn prevented the activation of JNK to protect cells. Our results showed that troxerutin enhanced radioprotection at least partially by activating AKT to inhibit the activation of JNK.

Keywords: AKT; JNK; PTEN; Thymus cell; Troxerutin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Enzyme Activation / drug effects
  • Enzyme Activation / radiation effects
  • Hydroxyethylrutoside / analogs & derivatives*
  • Hydroxyethylrutoside / pharmacology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Male
  • Mice
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Radiation-Protective Agents / pharmacology*
  • Thymus Gland / drug effects
  • Thymus Gland / pathology
  • Thymus Gland / radiation effects

Substances

  • Hydroxyethylrutoside
  • Radiation-Protective Agents
  • troxerutin
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases
  • PTEN Phosphohydrolase
  • Pten protein, mouse