HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents

PLoS ONE

Volumn 9, Issue 11, 2014, Pages

  McMahon, Michael ^a   Campbell, Kathryn H ^a   MacLeod, A Kenneth ^a   McLaughlin, Lesley A ^a   Henderson, Colin J ^a   Roland Wolf, C ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 (8 CYCLOPENTYL 7 ETHYL 5,6,7,8 TETRAHYDRO 5 METHYL 6 OXO 2 PTERIDINYLAMINO) 3 METHOXY N (1 METHYL 4 PIPERIDINYL)BENZAMIDE; ACROLEIN; BELINOSTAT; BEXAROTENE; CARMUSTINE; CHR 3531; ENTINOSTAT; EPIRUBICIN; HISTONE DEACETYLASE INHIBITOR; LOMUSTINE; MELPHALAN; NVP AEW 541; PANOBINOSTAT; PIM1 INHIBITOR 2; PROTEIN KINASE INHIBITOR; TACEDINALINE; TRANSCRIPTION FACTOR NRF2; TRICHOSTATIN A; UNCLASSIFIED DRUG; VORINOSTAT; ANTINEOPLASTIC AGENT; CYTOTOXIN; NFE2L2 PROTEIN, HUMAN; NVP-AEW541; PROTEIN KINASE PIM 1; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; SOMATOMEDIN C RECEPTOR;

AKR GENE; ARTICLE; CELL LINE; CELL VIABILITY ASSAY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG POTENCY; GENE; GENE INDUCTION; IMMUNOBLOTTING; LUCIFERASE ASSAY; MCF7 AREC32 CELL LINE; SIGNAL TRANSDUCTION; TUMOR CELL; ANTAGONISTS AND INHIBITORS; ANTIOXIDANT RESPONSIVE ELEMENT; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; NEOPLASMS; TUMOR CELL LINE;

ACROLEIN; ANTINEOPLASTIC AGENTS; ANTIOXIDANT RESPONSE ELEMENTS; CELL LINE, TUMOR; CYTOTOXINS; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONE DEACETYLASE INHIBITORS; HUMANS; NEOPLASMS; NF-E2-RELATED FACTOR 2; PROTO-ONCOGENE PROTEINS C-PIM-1; PYRIMIDINES; PYRROLES; RECEPTOR, IGF TYPE 1; SIGNAL TRANSDUCTION;

EID: 84913580308     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0114055     Document Type: Article

References (27)

1. Taguchi K, Motohashi H, Yamamoto M (2011) Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 16: 123-140. Available: http://www.ncbi.nlm.nih.gov/ pubmed/21251164. Accessed 31 March 2014.
2. Hayes JD, McMahon M (2009) NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci 34: 176-188. Available:, Go to ISI.://000265757600005.
3. Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, et al. (2004) Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate for proteasomal degradation of Nrf2. Mol Cell Biol 24: 7130-7139. Available:, Go to ISI.://000223045600022.
4. McMahon M, Lamont DJ, Beattie KA, Hayes JD (2010) Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc Natl Acad Sci U S A 107: 18838-18843. Available: http://www.pubmedcentral.nih.gov/articlerender. fcgi?artid52973898&tool5pmcentrez&rendertype5abstract. Accessed 2 November 2010.
5. Wolf CR (2001) Chemoprevention: increased potential to bear fruit. Proc Natl Acad Sci U S A 98: 2941-2943. Available: http://www.pubmedcentral.nih.gov/articlerender. fcgi?artid533333&tool5pmcentrez&rendertype5abstract.
6. Sporn M, Liby K (2012) NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer 3: 1-8. Available: http://dx.doi.org/10.1038/nrc3278. Accessed 3 October 2012.
7. Slocum SL, Kensler TW (2011) Nrf2: control of sensitivity to carcinogens. Arch Toxicol 85: 273-284. Available: http://www.ncbi.nlm.nih.gov/pubmed/21369766. Accessed 3 April 2011.
8. Hammerman PS, Lawrence MS, Voet D, Jing R, Cibulskis K, et al. (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489: 519-525. Available: http://www.nature.com/ doifinder/10.1038/nature11404. Accessed 9 September 2012.
9. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, et al. (2012) Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing. Cell 150: 1107-1120. Available: http://linkinghub.elsevier.com/retrieve/pii/S0092867412010616. Accessed 13 September 2012.
10. Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, et al. (2008) Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology 135: 1358-1368. Available:, Go to ISI.://000259982800043.
11. Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, et al. (2012) Article Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming. Cancer Cell 22: 66-79. Available: http://dx.doi.org/10.1016/j.ccr.2012.05.016.
12. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, et al. (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475: 106-109. Available: http://dx. doi.org/10.1038/nature10189. Accessed 31 March 2014.
13. Scha M, Farwanah H, Willrodt A, Huebner AJ, Sandhoff K, et al. (2012) Nrf2 links epidermal barrier function with antioxidant defense. EMBO Mol Med 4: 364-379. doi:10.1002/emmm.201200219.
14. Wang XJ, Hayes JD, Wolf CR (2006) Generation of a stable antioxidant response element-driven reporter gene cell line and its use to show redox-dependent activation of nrf2 by cancer chemotherapeutic agents. Cancer Res 66: 10983-10994. Available: http://www.ncbi.nlm.nih.gov/ pubmed/17108137. Accessed 8 August 2012.
15. McMahon M, Itoh K, Yamamoto M, Hayes JD (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem 278: 21592-21600. Available: http://www.ncbi.nlm.nih.gov/entrez/query. fcgi?cmd5Retrieve&db5PubMed&dopt5Citation&list-uids512682069.
16. MacLeod a K, McMahon M, Plummer SM, Higgins LG, Penning TM, et al. (2009) Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis 30: 1571-1580. Available: http:// www.ncbi.nlm.nih.gov/pubmed/19608619. Accessed 26 October 2012.
17. Connor TO, Ireland LS, Harrison DJ, Hayes JD (1999) Major differences exist in the function and tissue-specific expression of humn aldo-keto reductase AKR1 family members. Biochem J 504: 487-504.
18. McMahon M, Thomas N, Itoh K, Yamamoto M, John D, et al. (2006) Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a ''Tethering'' mechanism - A two-site interaction model for the Nrf2-Keap1 complex. J Biol Chem 281: 24756-24768. Available: http://www. ncbi.nlm.nih.gov/pubmed/16790436. Accessed 12 April 2013.
19. Gao X, Dinkova-Kostova a T, Talalay P (2001) Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphane. Proc Natl Acad Sci U S A 98: 15221-15226. Available: http://www. pubmedcentral.nih.gov/articlerender.fcgi?artid565010&tool5pmcentrez&rendertype5abstract.
20. Higgins LG, Kelleher MO, Eggleston IM, Itoh K, Yamamoto M, et al. (2009) Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents. Toxicol Appl Pharmacol 237: 267-280. Available: http://www.ncbi.nlm.nih.gov/pubmed/19303893. Accessed 31 October 2012.
21. Wang XJ, Hayes JD, Henderson CJ, Wolf CR (2007) Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Proc Natl Acad Sci U S A 104: 19589-19594. Available: http://www.pubmedcentral.nih.gov/articlerender. fcgi?artid52148333&tool5pmcentrez&rendertype5abstract.
22. Bailey-downs LC, Mitschelen M, Sosnowska D, Toth P, Pinto JT, et al. (2012) Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging. J Gerontol A Biol Sci Med Sci 67: 313-329. Available: http://www.pubmedcentral.nih.gov/articlerender. fcgi?artid53309870&tool5pmcentrez&rendertype5abstract. Accessed 17 May 2013.
23. Sun Z, Chin YE, Zhang DD (2009) Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response. Mol Cell Biol 29: 2658-2672. Available: http://www. pubmedcentral.nih.gov/articlerender.fcgi?artid52682049&tool5pmcentrez&rendertype5abstract. Accessed 26 April 2013.
24. Frew AJ, Johnstone RW, Bolden JE (2009) Enhancing the apoptotic and therapeutic effects of HDAC inhibitors. Cancer Lett 280: 125-133. Available: http://www.ncbi.nlm.nih.gov/pubmed/19359091. Accessed 12 March 2013.
25. Suzuki T, Motohashi H, Yamamoto M (2013) Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol Sci:1-7. Available: http://linkinghub.elsevier.com/retrieve/pii/S0165614713000667. Accessed 14 May 2013.
26. Strohecker AM, Guo JY, Karsli-Uzunbas G, Price SM, Chen GJ, et al. (2013) Autophagy Sustains Mitochondrial Glutamine Metabolism and Growth of BrafV600E-Driven Lung Tumors. Cancer Discov 3: 1272-1285. Available: http://www.ncbi.nlm.nih.gov/pubmed/23965987. Accessed 13 December 2013.
27. Mathijssen RHJ, Sparreboom A, Verweij J (2014) Determining the optimal dose in the development of anticancer agents. Nat Rev Clin Oncol Available: http://www.ncbi.nlm.nih.gov/pubmed/24663127. Accessed 26 March 2014.