The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression

Oncotarget

Volumn 6, Issue 7, 2015, Pages 4888-4900

  Zhang, Xiaolu ^a   Li, Bingnan ^a   de Jonge, Nick ^a   Björkholm, Magnus ^a   Xu, Dawei ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

AML; Apoptosis; DNMT inhibitors; Telomerase; Telomere; TERT

Indexed keywords

53BP1 PROTEIN; AZACITIDINE; DNA METHYLTRANSFERASE INHIBITOR; MARKER; MESSENGER RNA; TELOMERASE; TELOMERASE REVERSE TRANSCRIPTASE; UNCLASSIFIED DRUG; TERT PROTEIN, HUMAN;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; AGED; APOPTOSIS; ARTICLE; CANCER INHIBITION; CLINICAL ARTICLE; CONTROLLED STUDY; DNA DAMAGE; DNA METHYLATION; DOSE TIME EFFECT RELATION; DOWN REGULATION; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; LEUKEMIA CELL; MALE; MIDDLE AGED; PROTEIN LOCALIZATION; TELOMERE; TELOMERE SHORTENING; YOUNG ADULT; BIOSYNTHESIS; DRUG EFFECTS; GENETICS; LEUKEMIA, MYELOID, ACUTE; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

ADULT; AGED; APOPTOSIS; AZACITIDINE; CELL LINE, TUMOR; DNA DAMAGE; DNA METHYLATION; FEMALE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; TELOMERASE; TELOMERE; YOUNG ADULT;

EID: 84924973690     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2917     Document Type: Article

References (53)

1. Subramaniam D, Thombre R, Dhar A, Anant S. DNA Methyltransferases: A Novel Target for Prevention and Therapy. Front Oncol. 2014; 4:80.
2. Issa JP. Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection. Nat Clin Pract Oncol. 2005; 2 Suppl1:S24-29.
3. Issa JP, Kantarjian H. Azacitidine. Nat Rev Drug Discov. 2005; suppl:S6-7.
4. Mizuno S, Chijiwa T, Okamura T, Akashi K, Fukumaki Y, Niho Y, Sasaki H. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood. 2001; 97:1172-1179.
5. Raj K, John A, Ho A, Chronis C, Khan S, Samuel J, Pomplun S, Thomas NS, Mufti GJ. CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. Leukemia. 2007; 21:1937-1944.
6. Flotho C, Claus R, Batz C, Schneider M, Sandrock I, Ihde S, Plass C, Niemeyer CM, Lubbert M. The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009; 23:1019-1028.
7. Claus R, Lubbert M. Epigenetic targets in hematopoietic malignancies. Oncogene. 2003; 22:6489-6496.
8. Fandy T, Jiemjit A, Thakar M, Rhoden P, Suarez L, Gore S. Decitabine induces delayed reactive oxygen species (ROS) accumulation in leukemia cells and induces the expression of ROS generating enzymes. Clin Cancer Res. 2014; 20:1249-1258.
9. Tsai CT, Yang PM, Chern TR, Chuang SH, Lin JH, Klemm L, Muschen M, Chen CC. AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine. Oncotarget. 2014; 5:211-223.
10. Pinto AR, Li H, Nicholls C, Liu JP. Telomere protein complexes and interactions with telomerase in telomere maintenance. Front Biosci. 2011; 16:187-207.
11. Daniel M, Peek GW, Tollefsbol TO. Regulation of the human catalytic subunit of telomerase (hTERT). Gene. 2012; 498:135-146.
12. Xu D, Gruber A, Peterson C, Pisa P. Telomerase activity and the expression of telomerase components in acute myelogenous leukaemia. Br J Haematol. 1998; 102:1367-1375.
13. Kong F, Zheng C, Xu D. Telomerase as a "stemness" enzyme. Sci China Life Sci. 2014; 57:564-570.
14. Lansdorp PM. Telomeres, stem cells, and hematology. Blood. 2008; 111:1759-1766.
15. Ding D, Xi P, Zhou J, Wang M, Cong YS. Human telomerase reverse transcriptase regulates MMP expression independently of telomerase activity via NF-kappaB-dependent transcription. Faseb J. 2013; 27:4375-4383.
16. Cong Y, Shay JW. Actions of human telomerase beyond telomeres. Cell Res. 2008; 18:725-732.
17. Ghosh A, Saginc G, Leow SC, Khattar E, Shin EM, Yan TD, Wong M, Zhang Z, Li G, Sung WK. Telomerase directly regulates NF-kappaB-dependent transcription. Nat Cell Biol. 2012; 14:1270-1281.
18. Liu Z, Li Q, Li K, Chen L, Li W, Hou M, Liu T, Yang J, Lindvall C, Bjorkholm M, Jia J, Xu D. Telomerase reverse transcriptase promotes epithelial-mesenchymal transition and stem cell-like traits in cancer cells. Oncogene. 2013; 32:4203-4213.
19. Liu T, Liang X, Li B, Bjorkholm M, Jia J, Xu D. Telomerase reverse transcriptase inhibition stimulates cyclooxygenase 2 expression in cancer cells and synergizes with celecoxib to exert anti-cancer effects. Br J Cancer. 2013; 108:2272-2280.
20. Saretzki G. Extra-telomeric Functions of Human Telomerase: Cancer, Mitochondria and Oxidative Stress. Curr Pharm Des. 2014; 20:6386-403.
21. Singhapol C, Pal D, Czapiewski R, Porika M, Nelson G, Saretzki GC. Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosis. PLoS One. 2013; 8:e52989.
22. Nakamura M, Masutomi K, Kyo S, Hashimoto M, Maida Y, Kanaya T, Tanaka M, Hahn WC, Inoue M. Efficient inhibition of human telomerase reverse transcriptase expression by RNA interference sensitizes cancer cells to ionizing radiation and chemotherapy. Hum Gene Ther. 2005; 16:859-868.
23. Kanzawa T, Germano IM, Kondo Y, Ito H, Kyo S, Kondo S. Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide. Br J Cancer. 2003; 89:922-929.
24. Del Bufalo D, Rizzo A, Trisciuoglio D, Cardinali G, Torrisi MR, Zangemeister-Wittke U, Zupi G, Biroccio A. Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function. Cell Death Differ. 2005; 12:1429-1438.
25. Guilleret I, Benhattar J. Demethylation of the human telomerase catalytic subunit (hTERT) gene promoter reduced hTERT expression and telomerase activity and shortened telomeres. Exp Cell Res. 2003; 289:326-334.
26. Guilleret I, Yan P, Grange F, Braunschweig R, Bosman FT, Benhattar J. Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity. Int J Cancer. 2002; 101:335-341.
27. Dessain SK, Yu H, Reddel RR, Beijersbergen RL, Weinberg RA. Methylation of the human telomerase gene CpG island. Cancer Res. 2000; 60:537-541.
28. Devereux TR, Horikawa I, Anna CH, Annab LA, Afshari CA, Barrett JC. DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res. 1999; 59:6087-6090.
29. Li Y, Liu L, Andrews LG, Tollefsbol TO. Genistein depletes telomerase activity through cross-talk between genetic and epigenetic mechanisms. Int J Cancer. 2009; 125:286-296.
30. Borssen M, Cullman I, Noren-Nystrom U, Sundstrom C, Porwit A, Forestier E, Roos G. hTERT promoter methylation and telomere length in childhood acute lymphoblastic leukemia: associations with immunophenotype and cytogenetic subgroup. Exp Hematol. 2011; 39:1144-1151.
31. Kitagawa Y, Kyo S, Takakura M, Kanaya T, Koshida K, Namiki M, Inoue M. Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT. Clin Cancer Res. 2000; 6:2868-2875.
32. Tao SF, Zhang CS, Guo XL, Xu Y, Zhang SS, Song JR, Li R, Wu MC, Wei LX. Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells. World J Gastroenterol. 2012; 18:2334-2343.
33. Patel R, Shervington L, Lea R, Shervington A. Epigenetic silencing of telomerase and a non-alkylating agent as a novel therapeutic approach for glioma. Brain Res. 2008; 1188:173-181.
34. Pettigrew KA, Armstrong RN, Colyer HA, Zhang SD, Rea IM, Jones RE, Baird DM, Mills KI. Differential TERT promoter methylation and response to 5-aza-2'-deoxycytidine in acute myeloid leukemia cell lines: TERT expression, telomerase activity, telomere length, and cell death. Genes Chromosomes Cancer. 2012; 51:768-780.
35. Zhang ZX, Wang Y, Tao ZZ, Chen SM, Xiao BK, Zhou T. Subtelomeric demethylation deregulated hTERT expression, telomerase activity, and telomere length in four nasopharyngeal carcinoma cell lines. Cancer Biother Radiopharm. 2014; 29:289-294.
36. Grandjenette C, Schnekenburger M, Karius T, Ghelfi J, Gaigneaux A, Henry E, Dicato M, Diederich M. 5-aza-2'-deoxycytidine-mediated c-myc Down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia. Neoplasia. 2014; 16:511-528.
37. Jiemjit A, Fandy TE, Carraway H, Bailey KA, Baylin S, Herman JG, Gore SD. p21(WAF1/CIP1) induction by 5-azacytosine nucleosides requires DNA damage. Oncogene. 2008; 27:3615-3623.
38. Palii SS, Van Emburgh BO, Sankpal UT, Brown KD, Robertson KD. DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008; 28:752-771.
39. Gonzalo S, Jaco I, Fraga MF, Chen T, Li E, Esteller M, Blasco MA. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol. 2006; 8:416-424.
40. Buxton JL, Suderman M, Pappas JJ, Borghol N, McArdle W, Blakemore AI, Hertzman C, Power C, Szyf M, Pembrey M. Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci. Sci Rep. 2014; 4:4954.
41. Xu D, Gruber A, Bjorkholm M, Peterson C, Pisa P. Suppression of telomerase reverse transcriptase (hTERT) expression in differentiated HL-60 cells: regulatory mechanisms. Br J Cancer. 1999; 80:1156-1161.
42. Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer. 2008; 8:167-179.
43. Vera E, Canela A, Fraga MF, Esteller M, Blasco MA. Epigenetic regulation of telomeres in human cancer. Oncogene. 2008; 27:6817-6833.
44. Orta ML, Calderon-Montano JM, Dominguez I, Pastor N, Burgos-Moron E, Lopez-Lazaro M, Cortes F, Mateos S, Helleday T. 5-Aza-2'-deoxycytidine causes replication lesions that require Fanconi anemia-dependent homologous recombination for repair. Nucleic Acids Res. 2013; 41:5827-5836.
45. Graca I, Sousa EJ, Costa-Pinheiro P, Vieira FQ, Torres-Ferreira J, Martins MG, Henrique R, Jeronimo C. Anti-neoplastic properties of hydralazine in prostate cancer. Oncotarget. 2014; 5:311-320.
46. Fumagalli M, Rossiello F, Clerici M, Barozzi S, Cittaro D, Kaplunov JM, Bucci G, Dobreva M, Matti V, Beausejour CM. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol. 2012; 14:355-365.
47. Masutomi K, Possemato R, Wong JM, Currier JL, Tothova Z, Manola JB, Ganesan S, Lansdorp PM, Collins K, Hahn WC. The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc Natl Acad Sci U S A. 2005; 102:8222-8227.
48. Shin KH, Kang MK, Dicterow E, Kameta A, Baluda MA, Park NH. Introduction of human telomerase reverse transcriptase to normal human fibroblasts enhances DNA repair capacity. Clin Cancer Res. 2004; 10:2551-2560.
49. Li P, Hou M, Lou F, Bjorkholm M, Xu D. Telomere dysfunction induced by chemotherapeutic agents and radiation in normal human cells. Int J Biochem Cell Biol. 2012; 44:1531-1540.
50. Cesare AJ, Kaul Z, Cohen SB, Napier CE, Pickett HA, Neumann AA, Reddel RR. Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions. Nat Struct Mol Biol. 2009; 16:1244-1251.
51. Roos G, Hultdin M. Flow cytometric determination of telomere length. Cytometry. 2001; 45:79-80.
52. Baerlocher GM, Mak J, Tien T, Lansdorp PM. Telomere length measurement by fluorescence in situ hybridization and flow cytometry: tips and pitfalls. Cytometry. 2002; 47:89-99.
53. Ng LJ, Cropley JE, Pickett HA, Reddel RR, Suter CM. Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription. Nucleic Acids Res. 2009; 37:1152-1159.