Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways

References

• Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 May;71(3):209–249.
   PubMed Web of Science ®Google Scholar
• Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer. Lancet. 2020 Aug 29;396(10251):635–648.
   PubMed Web of Science ®Google Scholar
• Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019 Jan;18(1):41–58.
   PubMed Web of Science ®Google Scholar
• Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet. 2004 May 29;363(9423):1802–1811.
   PubMed Web of Science ®Google Scholar
• Capodanno D, Angiolillo DJ. Aspirin for primary cardiovascular risk prevention and beyond in diabetes mellitus. Circulation. 2016 Nov 15;134(20):1579–1594.
   PubMed Web of Science ®Google Scholar
• Johansson B. A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta Psychiatr Scand Suppl. 1992;369:15–26.
   PubMedGoogle Scholar
• Li H, Wang J, Wu C, et al. The combination of disulfiram and copper for cancer treatment. Drug Discov Today. 2020 Jun;25(6):1099–1108.
   PubMed Web of Science ®Google Scholar
• Guo F, Yang Z, Kulbe H, et al. Inhibitory effect on ovarian cancer ALDH+ stem-like cells by disulfiram and copper treatment through ALDH and ROS modulation. Biomed Pharmacother. 2019 Oct;118:109371.
   PubMed Web of Science ®Google Scholar
• Hassani S, Ghaffari P, Chahardouli B, et al. Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes. Biomed Pharmacother. 2018 Mar;99:561–569.
   PubMed Web of Science ®Google Scholar
• Li Y, Chen F, Chen J, et al. Disulfiram/Copper induces antitumor activity against both nasopharyngeal cancer cells and cancer-associated fibroblasts through ros/mapk and ferroptosis pathways. Cancers (Basel). 2020 Jan 6;12(1): 10.3390/cancers12010138.
   Web of Science ®Google Scholar
• Xu B, Wang S, Li R, et al. Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2. Cell Death Dis. 2017 May 18;8(5):e2797.
   PubMedGoogle Scholar
• Allensworth JL, Evans MK, Bertucci F, et al. Disulfiram (DSF) acts as a copper ionophore to induce copper-dependent oxidative stress and mediate anti-tumor efficacy in inflammatory breast cancer. Mol Oncol. 2015 Jun;9(6):1155–1168.
   PubMed Web of Science ®Google Scholar
• Guo W, Zhang X, Lin L, et al. The disulfiram/copper complex induces apoptosis and inhibits tumor growth in human osteosarcoma by activating the ROS/JNK signaling pathway. J Biochem. 2021 Apr 1;170:275–287.
   PubMed Web of Science ®Google Scholar
• Skrott Z, Mistrik M, Andersen KK, et al. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4. Nature. 2017 Dec 14;552(7684):194–199.
   PubMed Web of Science ®Google Scholar
• Yoshino H, Yamada Y, Enokida H, et al. Targeting NPL4 via drug repositioning using disulfiram for the treatment of clear cell renal cell carcinoma. PLoS One. 2020;15(7):e0236119.
   PubMed Web of Science ®Google Scholar
• Chen D, Cui QC, Yang H, et al. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006 Nov 1;66(21):10425–10433.
   PubMed Web of Science ®Google Scholar
• Koh HK, Seo SY, Kim JH, et al. Disulfiram, a re-positioned aldehyde dehydrogenase inhibitor, enhances radiosensitivity of human glioblastoma cells in vitro. Cancer Res Treat. 2019 Apr;51(2):696–705.
   PubMed Web of Science ®Google Scholar
• Majera D, Skrott Z, Chroma K, et al. Targeting the NPL4 adaptor of p97/VCP segregase by disulfiram as an emerging cancer vulnerability evokes replication stress and DNA damage while silencing the ATR pathway. Cells. 2020 Feb 18;9(2):469.
   PubMed Web of Science ®Google Scholar
• Sharma V, Verma V, Lal N, et al. Disulfiram and its novel derivative sensitize prostate cancer cells to the growth regulatory mechanisms of the cell by re-expressing the epigenetically repressed tumor suppressor-estrogen receptor β. Mol Carcinog. 2016 Nov;55(11):1843–1857.
   PubMed Web of Science ®Google Scholar
• Read E, Milford J, Zhu J, et al. The interaction of disulfiram and H(2)S metabolism in inhibition of aldehyde dehydrogenase activity and liver cancer cell growth. Toxicol Appl Pharmacol. 2021 Sep 1;426:115642
   PubMed Web of Science ®Google Scholar
• Zhou B, Guo L, Zhang B, et al. Disulfiram combined with copper induces immunosuppression via PD-L1 stabilization in hepatocellular carcinoma. Am J Cancer Res. 2019;9(11):2442–2455.
   PubMed Web of Science ®Google Scholar
• Qiu C, Zhang X, Huang B, et al. Disulfiram, a ferroptosis inducer, triggers lysosomal membrane permeabilization by up-regulating ROS in Glioblastoma. Onco Targets Ther. 2020;13:10631–10640.
   PubMed Web of Science ®Google Scholar
• Falls-Hubert KC, Butler AL, Gui K, et al. Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper. Free Radic Biol Med. 2020 Apr;150:1–11.
   PubMed Web of Science ®Google Scholar
• Zhang X, Hu P, Ding SY, et al. Induction of autophagy-dependent apoptosis in cancer cells through activation of ER stress: an uncovered anti-cancer mechanism by anti-alcoholism drug disulfiram. Am J Cancer Res. 2019;9(6):1266–1281.
   PubMed Web of Science ®Google Scholar
• Meraz-Torres F, Plöger S, Garbe C, et al. Disulfiram as a therapeutic agent for metastatic malignant melanoma-old myth or new logos? Cancers (Basel). 2020 Nov 27;12(12):3538.
   PubMed Web of Science ®Google Scholar
• Wang L, Chai X, Wan R, et al. Disulfiram chelated with copper inhibits the growth of gastric cancer cells by modulating stress response and Wnt/β-catenin signaling. Front Oncol. 2020;10:595718.
   PubMed Web of Science ®Google Scholar
• Zhang J, Pu K, Bai S, et al. The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways. J Int Med Res. 2020 Jun;48(6):300060520925996.
   PubMed Web of Science ®Google Scholar
• Park YM, Go YY, Shin SH, et al. Anti-cancer effects of disulfiram in head and neck squamous cell carcinoma via autophagic cell death. PLoS One. 2018;13(9):e0203069.
   PubMed Web of Science ®Google Scholar
• Liu P, Wang Z, Brown S, et al. Liposome encapsulated Disulfiram inhibits NFκB pathway and targets breast cancer stem cells in vitro and in vivo. Oncotarget. 2014 Sep 15;5(17):7471–7485.
   PubMedGoogle Scholar
• Menyhárt O, Nagy Á, Győrffy B. Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. R Soc Open Sci. 2018 Dec;5(12):181006.
   PubMed Web of Science ®Google Scholar
• Yip NC, Fombon IS, Liu P, et al. Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. Br J Cancer. 2011 May 10;104(10):1564–1574.
   PubMed Web of Science ®Google Scholar
• Li Y, Fu SY, Wang LH, et al. Copper improves the anti-angiogenic activity of disulfiram through the EGFR/Src/VEGF pathway in gliomas. Cancer Lett. 2015 Dec 1;369(1):86–96.
   PubMed Web of Science ®Google Scholar
• Xu Y, Zhou Q, Feng X, et al. Disulfiram/copper markedly induced myeloma cell apoptosis through activation of JNK and intrinsic and extrinsic apoptosis pathways. Biomed Pharmacother. 2020 Jun;126:110048.
   PubMed Web of Science ®Google Scholar
• Skrott Z, Majera D, Gursky J, et al. Disulfiram’s anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase. Oncogene. 2019 Oct;38(40):6711–6722.
   PubMed Web of Science ®Google Scholar
• Lu X, Lin B, Xu N, et al. Evaluation of the accumulation of disulfiram and its copper complex in A549 cells using mass spectrometry. Talanta. 2020 May 1;211:120732
   PubMed Web of Science ®Google Scholar
• Harris IS, DeNicola GM. The complex interplay between antioxidants and ROS in cancer. Trends Cell Biol. 2020 Jun;30(6):440–451.
   PubMed Web of Science ®Google Scholar
• Renaudin X. Reactive oxygen species and DNA damage response in cancer. Int Rev Cell Mol Biol. 2021;364:139–161.
   PubMed Web of Science ®Google Scholar
• Bartolacci C, Andreani C, El-Gammal Y, et al. Lipid metabolism regulates oxidative stress and ferroptosis in RAS-Driven cancers: a perspective on cancer progression and therapy. Front Mol Biosci. 2021;8:706650.
   PubMed Web of Science ®Google Scholar
• O’Brien P S, Xi Y, Miller JR, et al. Disulfiram (Antabuse) activates ROS-dependent ER stress and apoptosis in oral cavity squamous cell carcinoma. J Clin Med. 2019 May 6;8(5): 10.3390/jcm8050611.
   Web of Science ®Google Scholar
• Mouysset J, Deichsel A, Moser S, et al. Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for efficient DNA replication. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12879–12884.
   PubMed Web of Science ®Google Scholar
• Yu C, Huang X, Xu Y, et al. Lysosome dysfunction enhances oxidative stress-induced apoptosis through ubiquitinated protein accumulation in Hela cells. Anat Rec (Hoboken). 2013 Jan;296(1):31–39.
   PubMedGoogle Scholar
• Lu BS, Yin YW, Zhang YP, et al. Upregulation of NPL4 promotes bladder cancer cell proliferation by inhibiting DXO destabilization of cyclin D1 mRNA. Cancer Cell Int. 2019;19:149.
   PubMed Web of Science ®Google Scholar
• Liu X, Wang L, Cui W, et al. Targeting ALDH1A1 by disulfiram/copper complex inhibits non-small cell lung cancer recurrence driven by ALDH-positive cancer stem cells. Oncotarget. 2016 Sep 6;7(36):58516–58530.
   PubMedGoogle Scholar
• Lu C, Li X, Ren Y, et al. Disulfiram: a novel repurposed drug for cancer therapy. Cancer Chemother Pharmacol. 2021 Feb;87(2):159–172.
   PubMed Web of Science ®Google Scholar