Molecular mechanisms involved in the synergistic interaction of the EZH2 inhibitor 3-deazaneplanocin A with gemcitabine in pancreatic cancer cells

Molecular Cancer Therapeutics

Volumn 11, Issue 8, 2012, Pages 1735-1746

  Avan, Amir ^a   Crea, Francesco ^b   Paolicchi, Elisa ^b   Funel, Niccola ^b   Galvani, Elena ^a   Marquez, Victor E ^c   Honeywell, Richard J ^a   Danesi, Romano ^b   Peters, Godefridus J ^a   Giovannetti, Elisa ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF PISA   (Italy)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 DEAZANEPLANOCIN A; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; GEMCITABINE; HISTONE H3; MESSENGER RNA; TRANSCRIPTION FACTOR EZH2; UVOMORULIN;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENTIATION; HUMAN; HUMAN CELL; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ADENOSINE; ANTIGENS, CD; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; CADHERINS; CARCINOMA, PANCREATIC DUCTAL; CELL CYCLE; CELL LINE, TUMOR; CELL MOVEMENT; DEOXYCYTIDINE; DRUG SYNERGISM; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; GENE EXPRESSION; GENE EXPRESSION REGULATION, NEOPLASTIC; GLYCOPROTEINS; HUMANS; MEMBRANE TRANSPORT PROTEINS; PANCREATIC NEOPLASMS; PEPTIDES; POLYCOMB REPRESSIVE COMPLEX 2; SPHEROIDS, CELLULAR; TUMOR CELLS, CULTURED;

EID: 84864883108     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-12-0037     Document Type: Article

References (49)

1. Jemal A, Bray F, CenterMM,Ferlay J, Ward E, FormanD. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2. Ottenhof NA, de Wilde RF, Maitra A, Hruban RH, Offerhaus GJ. Molecular characteristics of pancreatic ductal adenocarcinoma. Patholog Res Int 2011;2011:620601.
3. Hamacher R, Schmid RM, Saur D, Schneider G. Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer 2008;7:64.
4. Duhagon MA, Hurt EM, Sotelo-Silveira JR, Zhang X, Farrar WL. Genomic profiling of tumor initiating prostatospheres. BMC Genomics 2010;11:324.
5. Gaviraghi M, Tunici P, Valensin S, Rossi M, Giordano C, Magnoni L, et al. Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells. Biosci Rep 2011;31:45-55.
6. Hong SP, Wen J, Bang S, Park S, Song SY. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int J Cancer 2009;125:2323-31.
7. Ottinger S, Klöppel A, Rausch V, Liu L, Kallifatidis G, Gross W, et al. Targeting of pancreatic and prostate cancer stem cell characteristics by Crambe crambe marine sponge extract. Int J Cancer 2012; 130:1671-81.
8. Rajeshkumar NV, Rasheed ZA, García-García E, López-Ríos F, Fujiwara K, Matsui WH, et al. A combination of DR5 agonistic monoclonal antibody with gemcitabine targets pancreatic cancer stem cells and results in long-term disease control in human pancreatic cancer model. Mol Cancer Ther 2010;9:2582-92.
9. Chang CJ, Yang JY, Xia W, Chen CT, Xie X, Chao CH, et al. EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-β-catenin signaling. Cancer Cell 2011;19:86-100.
10. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 2002;298:1039- 43.
11. Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006;16:871-74.
12. Santos-Rosa H, Caldas C. Chromatin modi fier enzymes, the histone code and cancer. Eur J Cancer 2005;41:2381-402. (Pubitemid 41540617)
13. Toll AD, Dasgupta A, Potoczek M, Yeo CJ, Kleer CG, Brody JR, et al. Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma. Hum Pathol 2010;41:1205-9.
14. Ougolkov AV, Bilim VN, Billadeau DD. Regulation of pancreatic tumor cell proliferation and chemoresistance by the histone methyltransferase EZH2. Clin Cancer Res 2008;14:6790-6.
15. Xiong HQ, Carr K, Abbruzzese JL. Cytotoxic chemotherapy for pancreatic cancer: advances to date and future directions. Drugs 2006;66:1059-72. (Pubitemid 43945867)
16. Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, et al. Pharmacologic disruption of polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 2007;21:1050-63. (Pubitemid 46686474)
17. Hayden A, Johnson P, Packham G, Crabb SJ. S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER2 inhibition. Breast Cancer Res Treat 2011;127:109-19.
18. Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res 2010;70: 4528 - 38.
19. Miranda TB, Cortez CC, Yoo CB, Liang G, Abe M, Kelly TK, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 2009;8:1579-88.
20. Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S, et al. Transcription analysis of human equilibrative nucleotide transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res 2006;66:3928-35.
21. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
22. Giovannetti E, Mey V, Danesi R, Basolo F, Barachini S, Deri M, et al. Interaction between gemcitabine and topotecan in human non-smallcell lung cancer cells: effects on cell survival, cell cycle and pharmacogenetic profile. Br J Cancer 2005;92:681-9. (Pubitemid 40460604)
23. Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malae-keh- Nikouei B. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharm Biol 2011;49:1039-45.
24. Mathews LA, Cabarcas SM, Hurt EM, Zhang X, Jaffee EM, Farrar WL. Increased expression of DNA repair genes in invasive human pancreatic cancer cells. Pancreas 2011;40:730-9.
25. Honeywell RJ, Giovannetti E, Peters GJ. Determination of the phosphorylated metabolites of gemcitabine and of difluorodeoxyuridine by LCMSMS. Nucleosides Nucleotides Nucleic Acids 2011;30:1203-13.
26. Yao J, Cai HH, Wei JS, An Y, Ji ZL, Lu ZP, et al. Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells. Oncol Rep 2010;23:1375 -82.
27. Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 2008;27:7274-84.
28. Padrón JM, van der Wilt CL, Smid K, Smitskamp-Wilms E, Backus HH, Pizao PE, et al. The multilayered postconfluent cell culture as a model for drug screening. Crit Rev Oncol Hematol 2000;36:141-57.
29. Xu CR, Cole PA, Meyers DJ, Kormish J, Dent S, Zaret KS. Chromatin "prepattern" and histone modifiers in a fate choice for liver and pancreas. Science 2011;332:963-6.
30. Chase A, Cross NC. Aberrations of EZH2 in cancer. Clin Cancer Res 2011;17:2613-8.
31. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002;419:624- 9.
32. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003;100:11606-11. (Pubitemid 37205983)
33. Chen Y, Xie D, Yin Li W, Man Cheung C, Yao H, Chan CY, et al. RNAi targeting EZH2 inhibits tumor growth and liver metastasis of pancreatic cancer in vivo. Cancer Lett 2010;297:109-16.
34. Zoabi M, Sadeh R, de Bie P, Marquez VE, Ciechanover A. PRAJA1 is a ubiquitin ligase for the polycomb repressive complex 2 proteins. Biochem Biophys Res Commun 2011;408:393-8.
35. Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, et al. miR-101 is down-regulated in glioblastoma resulting in EZH2- induced proliferation, migration, and angiogenesis. Oncotarget 2010;1:710-20.
36. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25.
37. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363:1049-57. (Pubitemid 38410779)
38. Gahr S, Ocker M, Ganslmayer M, Zopf S, Okamoto K, Hartl A, et al. The combination of the histone-deacetylase inhibitor trichostatin A and gemcitabine induces inhibition of proliferation and increased apoptosis in pancreatic carcinoma cells. Int J Oncol 2007;31:567-76.
39. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321:1801-6.
40. Kemp CD, Rao M, Xi S, Inchauste S, Mani H, Fetsch P, et al. Polycomb repressor complex-2 is a novel target for mesothelioma therapy. Clin Cancer Res 2012;18:77-90.
41. Aghdassi A, Sendler M, Guenther A, Mayerle J, Behn CO, Heidecke CD, et al. Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer. Gut 2012;61:439-48.
42. Simeone DM. Pancreatic cancer stem cells: implications for the treatment of pancreatic cancer. Clin Cancer Res 2008;14:5646-8.
43. Bao B, Ali S, Banerjee S, Wang Z, Logna F, Azmi AS, et al. Curcumin analog CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res 2012;72:335- 45.
44. Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, et al. Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. Mol Cancer 2011;10:40.
45. Rauchwerger DR, Firby PS, Hedley DW, Moore MJ. Equilibrativesensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res 2000;60:6075-9.
46. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, et al. Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol 2005;68:110-8. (Pubitemid 41002949)
47. Danesi R, Altavilla G, Giovannetti E, Rosell R. Pharmacogenomics of gemcitabine in non-small-cell lung cancer and other solid tumors. Pharmacogenomics 2009;10:69-80.
48. Van Moorsel CJ, Smid K, Voorn DA, Bergman AM, Pinedo HM, Peters GJ. Effect of gemcitabine and cis-platinum combinations on ribonucleotide and deoxyribonucleotide pools in ovarian cancer cell lines. Int J Oncol 2003;22:201-7.
49. Glazer RI, Knode MC, Tseng CK, Haines DR, Marquez VE. 3-Deazaneplanocin A: a new inhibitor of S-adenosylhomocysteine synthesis and its effects in human colon carcinoma cells. Biochem Pharmacol 1986;35:4523-7. (Pubitemid 17223288)