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Title: Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase.more » Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ;  [6] ;  [1]
  1. Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)
  2. Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)
  3. Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)
  4. Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)
  5. Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)
  6. Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)
Publication Date:
OSTI Identifier:
22416384
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 446; Journal Issue: 4; 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; CELL CYCLE; CELL PROLIFERATION; CHEMOTHERAPY; COLONY FORMATION; COPPER; COPPER COMPLEXES; GENES; GLIOMAS; IN VITRO; LUNGS; MAMMARY GLANDS; MESSENGER-RNA; PATIENTS; POLYMERASE CHAIN REACTION; PROSTATE; STEM CELLS