Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis

Sung, 2021, Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA A Cancer J. Clin., 71, 209, 10.3322/caac.21660

El-Serag, 2011, Hepatocellular carcinoma, N. Engl. J. Med., 365, 1118, 10.1056/NEJMra1001683

Siegel, 2018, Cancer statistics, CA A Cancer J. Clin., 68, 7, 10.3322/caac.21442

Manz, 2016, Iron and cancer: recent insights, Ann. N. Y. Acad. Sci., 1368, 149, 10.1111/nyas.13008

Hirschhorn, 2019, The development of the concept of ferroptosis, Free Radical Biol. Med., 133, 130, 10.1016/j.freeradbiomed.2018.09.043

Dixon, 2012, Ferroptosis: an iron-dependent form of nonapoptotic cell death, Cell, 149, 1060, 10.1016/j.cell.2012.03.042

Sun, 2016, Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells, Hepatology, 63, 173, 10.1002/hep.28251

Zhu, 2017, HSPA5 regulates ferroptotic cell death in cancer cells, Canc. Res., 77, 2064, 10.1158/0008-5472.CAN-16-1979

Poursaitidis, 2017, Oncogene-selective sensitivity to synchronous cell death following modulation of the amino acid nutrient cystine, Cell Rep., 18, 2547, 10.1016/j.celrep.2017.02.054

Doll, 2017, ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition, Nat. Chem. Biol., 13, 91, 10.1038/nchembio.2239

Llovet, 2008, Sorafenib in advanced hepatocellular carcinoma, N. Engl. J. Med., 359, 378, 10.1056/NEJMoa0708857

Zhai, 2013, Mechanisms of resistance to sorafenib and the corresponding strategies in hepatocellular carcinoma, World J. Hepatol., 5, 345, 10.4254/wjh.v5.i7.345

Frantzi, 2020, Drug repurposing in oncology, Lancet Oncol., 21, e543, 10.1016/S1470-2045(20)30610-0

Chen, 2006, 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, Canc. Res., 66, 10425, 10.1158/0008-5472.CAN-06-2126

Morrison, 2010, Disulfiram induces copper-dependent stimulation of reactive oxygen species and activation of the extrinsic apoptotic pathway in melanoma, Melanoma Res., 20, 11, 10.1097/CMR.0b013e328334131d

Qiu, 2020, Disulfiram, a ferroptosis inducer, triggers lysosomal membrane permeabilization by up-regulating ROS in glioblastoma, OncoTargets Ther., 13, 10631, 10.2147/OTT.S272312

Lin, 2011, Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth, Prostate, 71, 333, 10.1002/pros.21247

Zhang, 2010, Disulfiram treatment facilitates phosphoinositide 3-kinase inhibition in human breast cancer cells in vitro and in vivo, Canc. Res., 70, 3996, 10.1158/0008-5472.CAN-09-3752

Skrott, 2017, Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4, Nature, 552, 194, 10.1038/nature25016

Li, 2018, Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-β pathways, J. Cell Mol. Med., 22, 439, 10.1111/jcmm.13334

Chiba, 2014, Disulfiram eradicates tumor-initiating hepatocellular carcinoma cells in ROS-p38 MAPK pathway-dependent and -independent manners, PloS One, 9, 10.1371/journal.pone.0084807

Picard, 2018, An energetic view of stress, Focus on mitochondria, 49, 72

Li, 2020, Disulfiram/copper induces antitumor activity against both nasopharyngeal cancer cells and cancer-associated fibroblasts through ROS/MAPK and ferroptosis pathways, Cancers, 12, 138, 10.3390/cancers12010138

Sun, 2016, Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis, Hepatology, 64, 488, 10.1002/hep.28574

Bader, 2021, Activation of anti-oxidant Keap1/Nrf2 pathway modulates efficacy of dihydroartemisinin-based monotherapy and combinatory therapy with ionizing radiation, Free Radical Biol. Med., 168, 44, 10.1016/j.freeradbiomed.2021.03.024

Zhang, 2004, Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex, Mol. Cell Biol., 24, 10941, 10.1128/MCB.24.24.10941-10953.2004

Itoh, 1999, Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain, Gene Dev., 13, 76, 10.1101/gad.13.1.76

Ichimura, 2013, Phosphorylation of p62 activates the keap1-nrf2 pathway during selective autophagy, Mol. Cell., 51, 618, 10.1016/j.molcel.2013.08.003

Li, 2021, Sorafenib induces mitochondrial dysfunction and exhibits synergistic effect with cysteine depletion by promoting HCC cells ferroptosis, Biochem. Biophys. Res. Commun., 534, 877, 10.1016/j.bbrc.2020.10.083

Yuan, 2020, The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy, J. Hematol. Oncol., 13, 113, 10.1186/s13045-020-00949-4

Carneiro, 2020, Targeting apoptosis in cancer therapy, Nat. Rev. Clin. Oncol., 17

Du, 2020, Identification of Frataxin as a regulator of ferroptosis, Redox Biol, 32, 101483, 10.1016/j.redox.2020.101483

Bersuker, 2019, The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis, Nature, 575, 688, 10.1038/s41586-019-1705-2

Gao, 2019, Role of mitochondria in ferroptosis, Mol. Cell., 73, 354, 10.1016/j.molcel.2018.10.042

Ingold, 2018, Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis, Cell, 172, 409, 10.1016/j.cell.2017.11.048

Du, 2018, DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin, Free Radical Biol. Med., 131, 356, 10.1016/j.freeradbiomed.2018.12.011

Du, 2021, DHA exhibits synergistic therapeutic efficacy with cisplatin to induce ferroptosis in pancreatic ductal adenocarcinoma via modulation of iron metabolism, Cell Death Dis., 12, 705, 10.1038/s41419-021-03996-y

La Rosa, 2020, The Nrf2 induction prevents ferroptosis in Friedreich's Ataxia, Redox biology, 38, 101791, 10.1016/j.redox.2020.101791

Wang, 2021, GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis, Cell Death Dis., 12, 426, 10.1038/s41419-021-03718-4

Kerins, 2018, The roles of NRF2 in modulating cellular iron homeostasis, Antioxidants Redox Signal., 29, 1756, 10.1089/ars.2017.7176

Murakami, 2018, Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells, BMC Canc., 18, 680, 10.1186/s12885-018-4588-y

Zhou, 2012, Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease, Curr. Med. Chem., 19, 3523, 10.2174/092986712801323171

Li, 2021, Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma, Acta Pharmacol. Sin., 42, 301, 10.1038/s41401-020-0478-3