skip to main content

Title: Sensitization of cancer cells to radiation by selenadiazole derivatives by regulation of ROS-mediated DNA damage and ERK and AKT pathways

Highlights: • Selenadiazole derivatives could be used as an effective and low toxic sensitizer for radiotherapy. • Selenadiazole derivatives enhances radiation-induced growth inhibition on A375 cells through induction of G2/M arrest. • ROS-mediated signaling pathways play important roles in radiosensitization of selenadiazole derivatives. - Abstract: X-ray-based radiotherapy represents one of the most effective ways in treating human cancers. However, radioresistance and side effect remain as the most challenging issue. This study describes the design and application of novel selenadiazole derivatives as radiotherapy sensitizers to enhance X-ray-induced inhibitory effects on A375 human melanoma and Hela human cervical carcinoma cells. The results showed that, pretreatment of the cells with selenadiazole derivatives dramatically enhance X-ray-induced growth inhibition and colony formation. Flow cytometry analysis indicates that the sensitization by selenadiazole derivatives was mainly caused by induction of G2/M cell cycle arrest. Results of Western blotting demonstrated that the combined treatment-induced A375 cells growth inhibition was achieved by triggering reactive oxygen species-mediated DNA damage involving inactivation of AKT and MAPKs. Further investigation revealed that selenadiazole derivative in combination with X-ray could synergistically inhibit the activity of thioredoxin reductase-1 in A375 cells. Taken together, these results suggest that selenadiazole derivatives can act as novel radiosensitizer withmore » potential application in combating human cancers.« less
Authors:
 [1] ;  [2] ; ; ; ; ;  [1] ;  [1]
  1. Department of Chemistry, Jinan University, Guangzhou 510632 (China)
  2. (China)
Publication Date:
OSTI Identifier:
22416451
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 449; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AZOLES; BIOLOGICAL RADIATION EFFECTS; CELL CYCLE; COLONY FORMATION; DNA DAMAGES; HELA CELLS; HUMAN POPULATIONS; INACTIVATION; MELANOMAS; RADIOSENSITIVITY; RADIOTHERAPY; SENSITIZERS; TOXICITY; X RADIATION