title: Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.
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.
authors.affiliation: Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Lincan
authors.initials: L
authors.lastname: Duan
authors.affiliation: Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Guangqiang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Runxiang
authors.initials: R
authors.lastname: Yang
authors.affiliation: Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Congguo
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: daliduanlincan@163.com.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D003300:Copper; D002945:Cisplatin; D004221:Disulfiram
keywords: Copper; Disulfiram; MTT; NSCLC; Spheroids