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Inhibitory Effect of Disulfiram/Copper Complex on Non-small Cell Lung Cancer Cells.

Al's Comment:

 Although this project was not done for brain tumor cells, it illustrates a very important concept.  I hear of some of our members trying Disulfiram off label to treat their tumors.   There was also a project a while back that tested a copper restriction as a treatment for brain tumors.  So some members combined both.  However this study points out that in lung cancer cells (we do not know if it is true for brain), copper is needed to make the Disulfiram work.

  This points to the need to track people who try these combinations..  this is WHY we run the brain tumor virtual trial. Go to virtualtrials.com and click on Virtual trial for details and to join.  Everyone who has a brain tumor should participate.


Posted on: 03/27/2014

Biochem Biophys Res Commun. 2014 Mar 19. pii: S0006-291X(14)00489-6. doi: 10.1016/j.bbrc.2014.03.047. [Epub ahead of print]

Inhibitory Effect of Disulfiram/Copper Complex on Non-small Cell Lung Cancer Cells.

Duan L1, Shen H2, Zhao G1, Yang R3, Cai X4, Zhang L5, Jin C6, Huang Y7.

Author information:
1Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
2Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
3Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
4Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
5Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
6Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
7Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: daliduanlincan@163.com.

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. 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.

 


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