BIX-01294 induces autophagy-associated cell death via EHMT2/G9a dysfunction and intracellular reactive oxygen species production

Autophagy

Volumn 9, Issue 12, 2013, Pages 2126-2139

  Kim, Yunha ^a,d   Kim, Yong Sook ^a   Kim, Dong Eun ^a   Lee, Jee Suk ^a   Song, Ji Hoon ^a   Kim, Ha Gyeong ^a   Cho, Dong Hyung ^b   Jeong, Seong Yun ^a,c   Jin, Dong Hoon ^a   Jang, Se Jin ^c   Seol, Hyang Sook ^c   Suh, Young Ah ^a   Lee, Seung Jin ^a,e   Kim, Choung Soo ^a,c   Koh, Jae Young ^a   Hwang, Jung Jin ^a,c  

^a University of Ulsan College of Medicine   (South Korea)

^b Kyung Hee University   (South Korea)

^c Asan Medical Center   (South Korea)

^d Seoul National University College of Medicine   (South Korea)

^e Gachon University College of Medicine   (South Korea)

Author keywords

Autophagy; BIX 01294; EHMT2 G9a; Histone methyltransferase; ROS

Indexed keywords

3 METHYLADENINE; ACETYLCYSTEINE; AUTOPHAGY PROTEIN 5; BECLIN 1; CHLOROQUINE; DIPHENYLIODONIUM SALT; ESTROGEN RECEPTOR; GLUTATHIONE; GREEN FLUORESCENT PROTEIN; HYDROGEN PEROXIDE; MICROTUBULE ASSOCIATED PROTEIN 1; N (1 BENZYL 4 PIPERIDINYL) 2 (HEXAHYDRO 4 METHYL 1H 1,4 DIAZEPIN 1 YL) 6,7 DIMETHOXY 4 QUINAZOLINAMINE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SMALL INTERFERING RNA;

ARTICLE; AUTOPHAGY; BREAST CANCER; CANCER CELL; CANCER THERAPY; CELL ASSAY; CELL DEATH; CELL STRAIN HCT116; CELL STRAIN MCF 7; COLON CANCER; CONTROLLED STUDY; CYTOSOL; ENZYME ACTIVATION; HUMAN; HUMAN CELL; LIGHT CHAIN; OXIDATION REDUCTION POTENTIAL;

AUTOPHAGY; BIX-01294; EHMT2/G9A; HISTONE METHYLTRANSFERASE; ROS;

ANIMALS; AUTOPHAGY; AZEPINES; BREAST NEOPLASMS; CELLS, CULTURED; COLON; ENZYME INHIBITORS; FEMALE; HCT116 CELLS; HISTOCOMPATIBILITY ANTIGENS; HISTONE-LYSINE N-METHYLTRANSFERASE; HUMANS; MCF-7 CELLS; MICE; PRIMARY CELL CULTURE; QUINAZOLINES; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 84890834128     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.4161/auto.26308     Document Type: Article

References (51)

1. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010; 221:3-12; PMID:20225336; http://dx.doi.org/10.1002/ path.2697
2. Kondo Y, Kanzawa T, Sawaya R, Kondo S. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 2005; 5:726-34; PMID:16148885; http://dx.doi.org/10.1038/nrc1692
3. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451:1069-75; PMID:18305538; http://dx.doi.org/10.1038/nature06639
4. Dalby KN, Tekedereli I, Lopez-Berestein G, Ozpolat B. Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy 2010; 6:322-9; PMID:20224296; http://dx.doi.org/10.4161/ auto.6.3.11625
5. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Selfeating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8:741-52; PMID:17717517; http://dx.doi.org/10.1038/nrm2239
6. Roy S, Debnath J. Autophagy and tumorigenesis. Semin Immunopathol 2010; 32:383-96; PMID:20589500; http://dx.doi.org/10.1007/s00281-010-0213-0
7. Clarke PG, Puyal J. Autophagic cell death exists. Autophagy 2012; 8:867-9; PMID:22652592; http://dx.doi.org/10.4161/auto.20380
8. Huang J, Klionsky DJ. Autophagy and human disease. Cell Cycle 2007; 6:1837-49; PMID:17671424; http://dx.doi.org/10.4161/cc.6.15.4511
9. Portt L, Norman G, Clapp C, Greenwood M, Greenwood MT. Anti-apoptosis and cell survival: a review. Biochim Biophys Acta 2011; 1813:238-59; PMID:20969895; http://dx.doi.org/10.1016/j.bbamcr.2010.10.010
10. Wang RC, Wei Y, An Z, Zou Z, Xiao G, Bhagat G, White M, Reichelt J, Levine B. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science 2012; 338:956-9; PMID:23112296; http://dx.doi.org/10. 1126/science.1225967
11. Chen S, Rehman SK, Zhang W, Wen A, Yao L, Zhang J. Autophagy is a therapeutic target in anticancer drug resistance. Biochim Biophys Acta 2010; 1806:220-9; PMID:20637264
12. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003; 112:1809-20; PMID:14638851
13. Liu JJ, Lin M, Yu JY, Liu B, Bao JK. Targeting apoptotic and autophagic pathways for cancer therapeutics. Cancer Lett 2011; 300:105-14; PMID:21036469; http://dx.doi.org/10.1016/j.canlet.2010.10.001
14. Hwang JJ, Kim HN, Kim J, Cho DH, Kim MJ, Kim YS, Kim Y, Park SJ, Koh JY. Zinc(II) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line. Biometals 2010; 23:997-1013; PMID:20524045; http://dx.doi.org/10.1007/s10534-010-9346-9
15. Liu YL, Yang PM, Shun CT, Wu MS, Weng JR, Chen CC. Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. Autophagy 2010; 6:1057-65; PMID:20962572; http://dx.doi.org/10.4161/ auto.6.8.13365
16. Eskelinen EL. Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death. Cell Death Differ 2005; 12(Suppl 2):1468-72; PMID:16247492; http://dx.doi.org/10.1038/sj.cdd.4401721
17. Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, Kondo S. Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene 2005; 24:980-91; PMID:15592527; http://dx.doi.org/10.1038/sj.onc.1208095
18. Jänicke RU. MCF-7 breast carcinoma cells do not express caspase-3. Breast Cancer Res Treat 2009; 117:219-21; PMID:18853248; http://dx.doi.org/10. 1007/s10549-008-0217-9
19. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010; 140:313-26; PMID:20144757; http://dx.doi.org/10.1016/j. cell.2010.01.028
20. Chang Y, Zhang X, Horton JR, Upadhyay AK, Spannhoff A, Liu J, Snyder JP, Bedford MT, Cheng X. Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294. Nat Struct Mol Biol 2009; 16:312-7; PMID:19219047; http://dx.doi.org/10.1038/nsmb.1560
21. Huang J, Dorsey J, Chuikov S, Pérez-Burgos L, Zhang X, Jenuwein T, Reinberg D, Berger SL. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem 2010; 285:9636-41; PMID:20118233; http://dx.doi.org/10.1074/ jbc.M109.062588
22. Narlikar GJ, Fan HY, Kingston RE. Cooperation between complexes that regulate chromatin structure and transcription. Cell 2002; 108:475-87; PMID:11909519; http://dx.doi.org/10.1016/S0092-8674(02)00654-2
23. Strahl BD, Allis CD. The language of covalent histone modifications. Nature 2000; 403:41-5; PMID:10638745; http://dx.doi.org/10.1038/47412
24. Jenuwein T. The epigenetic magic of histone lysine methylation. FEBS J 2006; 273:3121-35; PMID:16857008; http://dx.doi.org/10.1111/j.1742-4658.2006. 05343.x
25. Varier RA, Timmers HT. Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta 2011; 1815:75-89; PMID:20951770
26. Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR, Issa JP. Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS One 2008; 3:e2037; PMID:18446223; http://dx.doi.org/10.1371/journal.pone.0002037
27. Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 2005; 6:838-49; PMID:16261189; http://dx.doi.org/10.1038/ nrm1761
28. Mund C, Lyko F. Epigenetic cancer therapy: Proof of concept and remaining challenges. Bioessays 2010; 32:949-57; PMID:21154865; http://dx.doi.org/10. 1002/bies.201000061
29. Chen MW, Hua KT, Kao HJ, Chi CC, Wei LH, Johansson G, Shiah SG, Chen PS, Jeng YM, Cheng TY, et al. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res 2010; 70:7830-40; PMID:20940408; http://dx.doi.org/10.1158/0008-5472. CAN-10-0833
30. Cho HS, Kelly JD, Hayami S, Toyokawa G, Takawa M, Yoshimatsu M, Tsunoda T, Field HI, Neal DE, Ponder BA, et al. Enhanced expression of EHMT2 is involved in the proliferation of cancer cells through negative regulation of SIAH1. Neoplasia 2011; 13:676-84; PMID:21847359
31. Kubicek S, O'Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML, Rea S, Mechtler K, Kowalski JA, Homon CA, et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 2007; 25:473-81; PMID:17289593; http://dx.doi.org/10.1016/j.molcel.2007.01.017
32. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol 2011; 7:566-74; PMID:21743462; http://dx.doi.org/10.1038/nchembio.599
33. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8:445-544; PMID:22966490; http://dx.doi.org/10.4161/auto.19496
34. Katayama H, Kogure T, Mizushima N, Yoshimori T, Miyawaki A. A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem Biol 2011; 18:1042-52; PMID:21867919; http://dx.doi.org/10.1016/ j.chembiol.2011.05.013
35. Jaber N, Dou Z, Chen JS, Catanzaro J, Jiang YP, Ballou LM, Selinger E, Ouyang X, Lin RZ, Zhang J, et al. Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Natl Acad Sci U S A 2012; 109:2003-8; PMID:22308354; http://dx.doi.org/10.1073/pnas.1112848109
36. Illner D, Zinner R, Handtke V, Rouquette J, Strickfaden H, Lanctôt C, Conrad M, Seiler A, Imhof A, Cremer T, et al. Remodeling of nuclear architecture by the thiodioxoxpiperazine metabolite chaetocin. Exp Cell Res 2010; 316:1662-80; PMID:20302859; http://dx.doi.org/10.1016/j.yexcr.2010.03.008
37. Lipinski MM, Hoffman G, Ng A, Zhou W, Py BF, Hsu E, Liu X, Eisenberg J, Liu J, Blenis J, et al. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Dev Cell 2010; 18:1041-52; PMID:20627085; http://dx.doi.org/10.1016/ j.devcel.2010.05.005
38. Webb JL, Ravikumar B, Rubinsztein DC. Microtubule disruption inhibits autophagosome-lysosome fusion: implications for studying the roles of aggresomes in polyglutamine diseases. Int J Biochem Cell Biol 2004; 36:2541-50; PMID:15325591; http://dx.doi.org/10.1016/j.biocel.2004.02.003
39. Geng Y, Kohli L, Klocke BJ, Roth KA. Chloroquine-induced autophagic vacuole accumulation and cell death in glioma cells is p53 independent. Neuro Oncol 2010; 12:473-81; PMID:20406898
40. Shi Y, Desponts C, Do JT, Hahm HS, Schöler HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 2008; 3:568-74; PMID:18983970; http://dx.doi.org/10.1016/j.stem.2008.10.004
41. Li W, Ding S. Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci 2010; 31:36-45; PMID:19896224; http://dx.doi.org/10.1016/j.tips.2009.10.002
42. Lakshmikuttyamma A, Scott SA, DeCoteau JF, Geyer CR. Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. Oncogene 2010; 29:576-88; PMID:19881540; http://dx.doi.org/10.1038/onc.2009.361
43. Isham CR, Tibodeau JD, Jin W, Xu R, Timm MM, Bible KC. Chaetocin: a promising new antimyeloma agent with in vitro and in vivo activity mediated via imposition of oxidative stress. Blood 2007; 109:2579-88; PMID:17090648; http://dx.doi.org/10.1182/blood-2006-07-027326
44. Tibodeau JD, Benson LM, Isham CR, Owen WG, Bible KC. The anticancer agent chaetocin is a competitive substrate and inhibitor of thioredoxin reductase. Antioxid Redox Signal 2009; 11:1097-106; PMID:18999987; http://dx.doi.org/10. 1089/ars.2008.2318
45. Azad MB, Chen Y, Gibson SB. Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. Antioxid Redox Signal 2009; 11:777-90; PMID:18828708; http://dx.doi.org/10.1089/ars.2008.2270
46. Robert T, Vanoli F, Chiolo I, Shubassi G, Bernstein KA, Rothstein R, Botrugno OA, Parazzoli D, Oldani A, Minucci S, et al. HDACs link the DNA damage response, processing of double-strand breaks and autophagy. Nature 2011; 471:74-9; PMID:21368826; http://dx.doi.org/10.1038/nature09803
47. Yoon YH, Cho KS, Hwang JJ, Lee SJ, Choi JA, Koh JY. Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells. Invest Ophthalmol Vis Sci 2010; 51:6030-7; PMID:20574031; http://dx.doi.org/10.1167/iovs.10-5278
48. Koh JY, Choi DW. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods 1987; 20:83-90; PMID:2884353; http://dx.doi.org/10.1016/0165- 0270(87)90041-0
49. Wilson EN, Bristol ML, Di X, Maltese WA, Koterba K, Beckman MJ, Gewirtz DA. A switch between cytoprotective and cytotoxic autophagy in the radiosensitization of breast tumor cells by chloroquine and vitamin D. Horm Cancer 2011; 2:272-85; PMID:21887591; http://dx.doi.org/10.1007/s12672-011-0081- 7
50. Cheng WT, Guo ZX, Lin CA, Lin MY, Tung LC, Fang K. Oxidative stress promotes autophagic cell death in human neuroblastoma cells with ectopic transfer of mitochondrial PPP2R2B (Bbeta2). BMC Cell Biol 2009; 10:91; PMID:20017961; http://dx.doi.org/10.1186/1471-2121-10-91
51. Morgan B, Sobotta MC, Dick TP. Measuring E(GSH) and H2O2 with roGFP2-based redox probes. Free Radic Biol Med 2011; 51:1943-51; PMID:21964034; http://dx.doi.org/10.1016/j.freeradbiomed.2011.08.035