Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy

Cancer Biology and Therapy

Volumn 3, Issue 11, 2004, Pages 1062-1068

  Gowher, Humaira ^a   Jeltsch, Albert ^a  

^a JACOBS UNIVERSITY BREMEN   (Germany)

Author keywords

dsRNA; Functional genomics; Gene silencing; RNA interference; siRNA; Therapeutic siRNAs

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 5 METHYLCYTIDINE; 5,6 DIHYDROAZACITIDINE; AZACITIDINE; CISPLATIN; CYTIDINE DERIVATIVE; DNA; DNA METHYLTRANSFERASE; DOXORUBICIN; FLUCYTOSINE DEOXYRIBOSIDE; PSEUDOISOCYTIDINE; UNCLASSIFIED DRUG; ZEBULARINE; CYTIDINE; DNA (CYTOSINE 5) METHYLTRANSFERASE; DRUG DERIVATIVE;

CANCER; CANCER THERAPY; CHEMICAL STRUCTURE; CHEMISTRY; CLINICAL TRIAL; DNA METHYLATION; DRUG ACTIVITY; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME MECHANISM; HUMAN; INHIBITION KINETICS; PROTEIN TARGETING; REACTION ANALYSIS; REVIEW; ANIMAL; DRUG ANTAGONISM; GENETICS; METABOLISM; NEOPLASM;

ANIMALS; CYTIDINE; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; HUMANS; NEOPLASMS;

EID: 22144461094     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.3.11.1308     Document Type: Review

References (66)

1. Jones PA. DNA methylation and cancer. Oncogene 2002; 21:5358-60.
2. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004; 4:143-53.
3. Jeltsch A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chembiochem 2002; 3:274-93.
4. Jaenisch R, Bird A. Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nat Genet 2003; 33:245-54.
5. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001; 293:1068-70.
6. Meehan RR, Stancheva I. DNA methylation and control of gene expression in vertebrate development. Essays Biochem 2001; 37:59-70.
7. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16:6-21.
8. Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 2002; 3:662-73.
9. Ehrlich M. Expression of various genes is controlled by DNA methylation during mammalian development. J Cell Biochem 2003; 88:899-910.
10. Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature 1997; 386:623-7.
11. Murphy SK, Jirtle RL. Imprinting evolution and the price of silence. Bioessays 2003; 25:577-88.
12. Chow JC, Brown CJ. Forming facultative heterochromatin: Silencing of an X chromosome in mammalian females. Cell Mol Life Sci 2003; 60:2586-603.
13. Okamoto I, Otte AP, Allis CD, Reinberg D, Heard E. Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 2004; 303:644-9.
14. Yoder JA, Soman NS, Verdine GL, Bestor TH. DNA (cytosine-5)- methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J. Mol Biol 1997; 270:385-95.
15. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429:457-63.
16. Feinberg AP, Cui H, Ohlsson R. DNA methylation and genomic imprinting: Insights from cancer into epigenetic mechanisms. Semin Cancer Biol 2002; 12:389-98.
17. Klimasauskas S, Kumar S, Roberts RJ, Cheng X. HhaI methyltransferase flips its target base out of the DNA helix. Cell 1994; 76:357-69.
18. Cheng X, Blumenthal RM. S-adenosylmethionine-dependent methyltransferases: Structures and functions. Singapore: World Scientific Publishing, 1999.
19. O'Gara M, Klimasauskas S, Roberts RJ, Cheng X. Enzymatic C5-cytosine methylation of DNA: Mechanistic implications of new crystal structures for HhaI methyltransferase-DNA-AdoHcy complexes. J Mol Biol 1996; 261:634-45.
20. Santi DV. Mechanistic studies of RNA modifying enzymes. RNA pseudouridine synthase and m5cytosine methyl transferase. Nucleic Acids Symp Ser 2000; 147-8.
21. Finer-Moore JS, Santi DV, Stroud RM. Lessons and conclusions from dissecting the mechanism of a bisubstrate enzyme: Thymidylate synthase mutagenesis, function, and structure. Biochemistry 2003; 42:248-56.
22. Roberts RJ, Cheng X. Base flipping. Annu Rev Biochem 1998; 67:181-98.
23. Cheng X, Roberts RJ. AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucleic Acids Res 2001; 29:3784-95.
24. Reinisch KM, Chen L, Verdine GL, Lipscomb WN. The crystal structure of HaeIII methyltransferase convalently complexed to DNA: An extrahelical cytosine and rearranged base pairing. Cell 1995; 82:143-53.
25. Wyszynski MW, Gabbara S, Kubareva EA, Romanova EA, Oretskaya TS, Gromova ES, Shabarova ZA, Bhagwat AS. The cysteine conserved among DNA cytosine methylases is required for methyl transfer, but not for specific DNA binding. Nucleic Acids Res 1993; 21:295-301.
26. Hanck T, Schmidt S, Fritz HJ. Sequence-specific and mechanism-based crosslinking of Dcm DNA cytosine-C5 methyltransferase of E. coli K-12 to synthetic oligonucleotides containing 5-fluoro-2′-deoxycytidine. Nucleic Acids Res 1993; 21:303-9.
27. Reither S, Li F, Gowher H, Jeltsch A. Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: Covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme. J Mol Biol 2003; 329:675-84.
28. Wilke K, Rauhut E, Noyer-Weidner M, Lauster R, Pawlek B, Behrens B, et al. Sequential order of target-recognizing domains in multispecific DNA-methyltransferases. EMBO J 1988; 7:2601-9.
29. Mi S, Roberts RJ. The DNA binding affinity of HhaI methylase is increased by a single amino acid substitution in the catalytic center. Nucleic Acids Res 1993; 21:2459-64.
30. Christman JK. 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: Mechanistic studies and their implications for cancer therapy. Oncogene 2002; 21:5483-95.
31. Momparler RL, Cote S, Eliopoulos N. Pharmacological approach for optimization of the dose schedule of 5-Aza-2′-deoxycytidine (Decitabine) for the therapy of leukemia. Leukemia 1997; 11:S1-6.
32. Wijermans P, Lubbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A. Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 2000; 18:956-62.
33. Leone G, Voso MT, Teofili L, Lubbert M. Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol 2003; 109:89-102.
34. Schmitt CA, Lowe SW. Apoptosis and therapy. J Pathol 1999; 187:127-37.
35. Teitz T, Wei T, Valentine MB, Vanin EF, Grenet J, Valentine VA, Behm FG, Look AT, Lahti JM, Kidd VJ. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med 2000; 6:529-35.
36. Fulda S, Kufer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B, Debatin KM. Sensitization for death receptor- or drug-induced apoptosis by reexpression of caspase-8 through demethylation or gene transfer. Oncogene 2001; 20:5865-77.
37. Worm J, Kirkin AF, Dzhandzhugazyan KN, Guldberg P. Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate- resistant human breast cancer cells. J Biol Chem 2001; 276:39990-40000.
38. Constantinides PG, Jones PA, Gevers W. Functional striated muscle cells from nonmyoblast precursors following 5-azacytidine treatment. Nature 1977; 267:364-6.
39. Chou TC, Burchenal JH, Fox JJ, Watanabe KA, Chu CK, Philips FS. Metabolism and effects of 5-(beta-D-ribofuranosyl)isocytosine in P815 cells. Cancer Res 1979; 39:720-8.
40. Beisler JA, Abbasi MM, Driscoll JS. Dihydro-5-azacytidine hydrochloride, a biologically active and chemically stable analog of 5-azacytidine. Cancer Treat Rep 1976; 60:1671-4.
41. Kelley JA, Driscoll JS, McCormack JJ, Roth JS, Marquez VE. Furanose-pyranose isomerization of reduced pyrimidine and cyclic urea ribosides. J Med Chem 1986; 29:2351-8.
42. Kim CH, Marquez VE, Mao DT, Haines DR, McCormack JJ. Synthesis of pyrimidin-2-one nucleosides as acid-stable inhibitors of cytidine deaminase. J Med Chem 1986; 29:1374-80.
43. Laliberte J, Marquez VE, Momparler RL. Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2′-deoxycytidine by human cytidine deaminase. Cancer Chemother Pharmacol 1992; 30:7-11.
44. Gonzalgo ML, Hayashida T, Bender CM, Pao MM, Tsai YC, Gonzales FA, Nguyen HD, Nguyen TT, Jones PA. The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. Cancer Res 1998; 58:1245-52.
45. Driscoll JS, Marquez VE, Plowman J, Liu PS, Kelley JA, Barchi Jr JJ. Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogues. J Med Chem 1991; 34:3280-4.
46. Hurd PJ, Whitmarsh AJ, Baldwin GS, Kelly SM, Waltho JP, Price NC, Connolly BA, Hornby DP. Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. J Mol Biol 1999; 286:389-401.
47. Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ, Hornby DP. Zebularine: A novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol 2002; 321:591-9.
48. Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell 1980; 20:85-93.
49. Boothman DA, Briggle TV, Greer S. Exploitation of elevated pyrimidine deaminating enzymes for selective chemotherapy. Pharmacol Ther 1989; 42:65-88.
50. Santi DV, Norment A, Garrett CE. Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci USA 1984; 81:6993-7.
51. Friedman S. The irreversible binding of azacytosine-containing DNA fragments to bacterial DNA(cytosine-5)methyltransferases. J Biol Chem 1985; 200:5698-705.
52. Friedman S. Binding of the EcoRII methylase to azacytosine-containing DNA. Nucleic Acids Res 1986; 14:4543-56.
53. Gabbara S, Sheluho D, Bhagwat AS. Cytosine methyltransferase from Escherichia coli in which active site cysteine is replaced with serine is partially active. Biochemistry 1995; 34:8914-23.
54. Brank AS, Eritja R, Garcia RG, Marquez VE, Christman JK. Inhibition of HhaI DNA (Cytosine-C5) methyltransferase by oligodeoxyribonucleotides containing 5-aza-2′-deoxycytidine: Examination of the intertwined roles of cofactor, target, transition state structure and enzyme conformation. J Mol Biol 2002; 323:53-67.
55. Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci USA 1994; 91:11797-801.
56. Osterman DG, DePillis GD, Wu JC, Matsuda A, Santi DV. 5-Fluorocytosine in DNA is a mechanism-based inhibitor of HhaI methylase. Biochemistry 1988; 27:5204-5210.
57. Chen L, MacMillan AM, Chang W, Ezaz-Nikpay K, Lane WS, Verdine GL. Direct identification of the active-site nucleophile in a DNA (Cytosine-5)- methyltransferase. Biochemistry 1991; 30:11018-11025.
58. Taylor C, Ford K, Connolly BA, Hornby DP. Determination of the order of substrate addition to MspI DNA methyltransferase using a novel mechanism-based inhibitor. Biochem J 1993; 291:493-504.
59. Ford K, Taylor C, Connolly B, Hornby DP. Effects of cofactor and deoxycytidine substituted oligonucleotides upon sequence-specific interactions between MspI DNA methyltransferase and DNA. J Mol Biol 1993; 230:779-86.
60. Baldwin GS, Kelly SM, Price NC, Wilson GW, Connolly BA, Artymiuk PJ, Hornby DP. Ligand-induced conformational states of the cytosine-specific DNA methyltransferase M.HgaI-2. J Mol Biol 1994; 235:545-53.
61. Subach OM, Khoroshaev AV, Gerasimov DN, Baskunov VB, Shchyolkina AK, Gromova ES. 2-Pyrimidinone as a probe for studying the EcoRII DNA methyltransferase-substrate interaction. Eur J Biochem 2004; 271:2391-9.
62. Pradhan S, Adams RL. Distinct CG and CNG DNA methyltransferases in Pisum sativum. Plant J 1995; 7:471-81.
63. Marquez VE, Eritja R, Kelley JA, Vanbemmel D, Christman JK. Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (zebularine) at the GCGC recognition domain. Ann NY Acad Sci 2003; 1002:154-64.
64. Sharath AN, Weinhold E, Bhagwat AS. Reviving a dead enzyme: Cytosine deaminations promoted by an inactive DNA methyltransferase and an S-adenosylmethionine analogue. Biochemistry 2000; 39:14611-6.
65. Yan L, Nass SJ, Smith D, Nelson WG, Herman JG, Davidson NE. Specific inhibition of DNMT1 by antisense oligonucleotides induces reexpression of estrogen receptor-alpha (ER) in ER-negative human breast cancer cell lines. Cancer Biol Ther 2003; 2:552-6.
66. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, Leonhardt H, Jaenisch R. Induction of tumors in mice by genomic hypomethylation. Science 2003; 300:489-92.