Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation

Molecular Cancer

Volumn 9, Issue , 2010, Pages

  Gravina, Giovanni L ^a   Festuccia, Claudio ^a   Marampon, Francesco ^a,b   Popov, Vladimir M ^b   Pestell, Richard G ^b   Zani, Bianca M ^a   Tombolini, Vincenzo ^a  

^a UNIVERSITY OF L'AQUILA   (Italy)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; AZACITIDINE; CISPLATIN; DNA METHYLTRANSFERASE INHIBITOR; DOXORUBICIN; EPIGALLOCATECHIN GALLATE; MG 98; N PHTHALOYLTRYPTOPHAN; PROCAINAMIDE; TEMOZOLOMIDE; ZEBULARINE; DNA METHYLTRANSFERASE; ENZYME INHIBITOR;

APOPTOSIS; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CLINICAL TRIAL; DNA DAMAGE; DNA METHYLATION; DNA REPAIR; DRUG MECHANISM; HUMAN; IONIZING RADIATION; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; REVIEW; ANIMAL; DRUG ANTAGONISM; DRUG EFFECT; GENETIC EPIGENESIS; METABOLISM; NEOPLASM;

ANIMALS; DNA MODIFICATION METHYLASES; ENZYME INHIBITORS; EPIGENESIS, GENETIC; HUMANS; NEOPLASMS; RADIATION, IONIZING;

EID: 78649327715     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-9-305     Document Type: Review

References (192)

1. Horn PJ, Peterson CL. Heterochromatin assembly: A new twist on an old model. Chromosome Res 2006, 14:83-94. 10.1007/s10577-005-1018-1, 16506098.
2. Luger K. Structure and dynamic behavior of nucleosomes. Curr Opin Genet Dev 2003, 13:127-135. 10.1016/S0959-437X(03)00026-1, 12672489.
3. Saha A, Wittmeyer J, Cairns BR. Chromatin remodelling: The industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 2006, 7:437-47. 10.1038/nrm1945, 16723979.
4. Marks PA, Rifkind RA, Richon VM, Breslow R. Inhibitors of histone deacetylase are potentially effective anticancer agents. Clin Cancer Res 2001, 7:759-60.
5. Iizuka M, Smith MM. Functional consequences of histone modifications. Curr Opin Genet Dev 2003, 13:154-60. 10.1016/S0959-437X(03)00020-0, 12672492.
6. Spotswood HT, Turner BM. An increasingly complex code. J Clin Invest 2002, 110:577-82. 151116, 12208855.
7. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002, 16:6-21. 10.1101/gad.947102, 11782440.
8. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002, 3:415-428. 10.1038/nrg962, 12042769.
9. Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet 2000, 9:2395-2402. 10.1093/hmg/9.16.2395, 11005794.
10. Okano M. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 1999, 99:247-257. 10.1016/S0092-8674(00)81656-6, 10555141.
11. Okano M. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 1998, 19:219-220. 10.1038/890, 9662389.
12. Rhee I. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 2002, 416:552-556. 10.1038/416552a, 11932749.
13. Rhee I. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 2000, 404:1003-1007. 10.1038/35010000, 10801130.
14. Gravina GL, Festuccia C, Millimaggi D, Dolo V, Tombolini V, De Vito M. Chronic Azacitidine Treatment Results in Differentiating Effects, Sensitizes Against Bicalutamide in Androgen-Independent Prostate Cancer Cells. The Prostate 2008, 68:793-801. 10.1002/pros.20748, 18324645.
15. Herman JG, Baylin SB. Gene silencing in cancer in association with promoterhypermethylation. N Engl J Med 2003, 349:2042-2054. 10.1056/NEJMra023075, 14627790.
16. Silverman LR, Demakos EP, Peterson BL. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002, 20:2429-40. 10.1200/JCO.2002.04.117, 12011120.
17. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999, 21:103-7. 10.1038/5047, 9916800.
18. kristensen LS, Nielsen HM, Hansen LL. Epigenetic and cancer treatment. European Juornal of Pharmacology 2009, 625:131-142.
19. Oki Y, Aoki E, Issa JP. Decitabine--Bedside to bench. Crit Rev Oncol 2007, 61:140-152.
20. Larsen AK, Escargueil AE, Skladanowski A. Resistance mechanisms associated with altered intracellular distribution of anticancer agents. Pharmacol Ther 2000, 85:217-29. 10.1016/S0163-7258(99)00073-X, 10739876.
21. Larsen AK, Skladanowski A. Cellular resistance to topoisomerase-targeted drugs: from drug uptake to cell death. Biochim Biophys Acta 1998, 1400:257-74.
22. Kern MA, Helmbach H, Artuc M, Karmann D, Jurgovsky K, Schadendorf D. Human melanoma cell lines selected in vitro displaying various levels of drug resistance against Cisplatin, fotemustine, vindesine or Etoposide: modulation of proto-oncogene expression. Anticancer Res 1997, 17:4359-70.
23. Spitz DR, Kinter MT, Roberts RJ. Contribution of increased glutathione content to mechanisms of oxidative stress resistance in hydrogen peroxide resistant hamster fibroblasts. J Cell Physiol 1995, 165:600-9. 10.1002/jcp.1041650318, 7593239.
24. Spitz DR, Li GC. Heat-induced cytotoxicity in H2O2-resistant Chinese hamster fibroblasts. J Cell Physiol 1990, 142:255-60. 10.1002/jcp.1041420206, 2303525.
25. Spitz DR, Phillips JW, Adams DT, Sherman CM, Deen DF, Li GC. Cellular resistance to oxidative stress is accompanied by resistance to Cisplatin: the significance of increased catalase activity and total glutathione in hydrogen peroxide-resistant fibroblasts. J Cell Physiol 1993, 156:72-9. 10.1002/jcp.1041560111, 8314861.
26. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 1997, 15:356-362. 10.1038/ng0497-356, 9090379.
27. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943-1947. 10.1126/science.275.5308.1943, 9072974.
28. Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Cancer Res 1997, 57:4183-4186.
29. Guldberg P, thor Straten P, Birck A, Ahrenkiel V, Kirkin AF, Zeuthen J. Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 1997, 57:3660-3663.
30. Cairns P, Okami K, Halachmi S, Halachmi N, Esteller M, Herman JG, Jen J, Isaacs WB, Bova GS, Sidransky D. Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 1997, 57:4997-5000.
31. Gravina G, Biordi L, Martella F, Flati V, Ricevuto E, Ficorella C, Tombolini V, Festuccia C. Epigenetic modulation of PTEN expression during antiandrogenic therapies in human prostate cancer. International Journal of Oncology 2009, 35:1133-9.
32. Soria JC, Lee HY, Lee JI, Wang L, Issa JP, Kemp BL, Liu DD, Kurie JM, Mao L, Khuri FR. Lack of PTEN Expression in Non-Small Cell Lung Cancer Could Be Related to Promoter Methylation. Clin Cancer Res 2002, 8:1178-1184.
33. Whang YE, Wu X, Suzuki H. Inactivation of the tumor suppressor PTENyMMAC1 in dvanced human prostate cancer through loss of expression. Proc Natl Acad Sci 1998, 95:5246-5250. 10.1073/pnas.95.9.5246, 20246, 9560261.
34. Davies MA, Koul D, Dhesi H, Berman R, McDonnell TJ. Regulation of AKT/PKB activity, cellular growth, and apoptosis in prostate carcinomacells by MMAC/PTEN. Cancer Res 1999, 59:2551-2556.
35. Festuccia C, Gravina GL, D'Alessandro AM, Muzi P, Millimaggi D. Azacitidine improves antitumor effects of docetaxel and cisplatin in aggressive prostate cancer models. Endocr Relat Cancer 2009, 16:401-413. 10.1677/ERC-08-0130, 19153211.
36. Tanaka M, Koul D, Davies MA, Liebert M, Steck PA, Grossman BH. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Oncogene 2000, 19:5406-5412. 10.1038/sj.onc.1203918, 11103942.
37. Fujiwara T, Grimm EA, Mukhopadnyay T, Zhang WW. Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild type p53 gene. Cancer Res 1994, 54:2287-2291.
38. Ogawa N, Fujiwara T, Kagawa S. Novel combination therapy for human colon cancer with adenovirus-mediated wild-type p53 gene transfer and DNA-damaging chemotherapeutic agent. Int J Cancer 1997, 73:367-70. 10.1002/(SICI)1097-0215(19971104)73:3<367::AID-IJC11>3.0.CO;2-A, 9359484.
39. Gurnani M, Lipari P, Dell J, Shi B, Nielsen LL. Adenovirus-mediated p53 gene therapy has greater efficacy when combined with chemotherapy against human head-neck, ovarian, prostate, and breast cancer. Cancer Chemother Pharmacol 1999, 44:143-151. 10.1007/s002800050959, 10412949.
40. Thoretsky JA, Takar M, Eskenazi AE, Frantz CN. Phosphoinositide 3-hydroxide kinase blockade enhances apoptosis in the Ewing's sarcoma family tumors. Cancer Res 1999, 59:5745-50.
41. Wan X, Li J, Lu X. PTEN augments doxorubicin-induced apoptosis in PTEN-null Ishikawa cells. Int J Gynecol Cancer 2007, 17:808-812. 10.1111/j.1525-1438.2007.00890.x, 17359293.
42. Mayo LD, Dixon JE, Durden DL, Tonks NK, Donner DB. PTEN protects p53from Mdm2 and sensitizes cancer cells to chemotherapy. J Biol Chem 2002, 277:5484-9. 10.1074/jbc.M108302200, 11729185.
43. Green SK, Frankel A, Kerbel RS. Adhesion-dependent multicellular drug resistance. Anti-Cancer Drug Design 1999, 14:153-68.
44. St Croix B, Rak JW, Kapitain S, Sheehan C, Graham CH, Kerbel RS. Reversal by hyaluronidase of adhesion-dependent multicellular drug resistance in mammary carcinoma cells. J Natl Cancer Inst 1996, 88:1285-96. 10.1093/jnci/88.18.1285, 8797768.
45. St Croix B, Florenes VA, Rak JW, Flanagan M, Bhattacharya N, Slingerland JM, Kerbel RS. Impact of the cyclin dependent kinase inhibitor p27Kip1 on adhesion-dependent resistance of tumor cells to anticancer agents. Nat Med 1996, 2:1204-10. 10.1038/nm1196-1204, 8898746.
46. St Croix B, Sheehan C, Rak JW, Florenes VA, Slingerland JM, Kerbel RS. E-cadherin-dependent growth suppression is mediated by the cyclin dependent kinase inhibitor p27KIP1. J Cell Biol 1998, 142:557-71. 10.1083/jcb.142.2.557, 2133056, 9679152.
47. Green SK, Francia G, Isidoro C, Kerbel RS. Anti-adhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro. Mol Cancer Ther 2004, 3:149-59.
48. Teicher BA, Herman TS, Holden SA, Wang YY, Pfeffer MR, Crawford JW, Frei E. Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science 1990, 247:1457-61. 10.1126/science.2108497, 2108497.
49. Youn CK, Cho HJ, Kim SH, Kim HB, Kim MH, Chang IY, Lee JS, Chung MH, Hahm KS, You HJ. Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity. Nat Cell Biol 2005, 7:137-47. 10.1038/ncb1215, 15619620.
50. Kobayashi H, Man S, Kapitain SJ, Teicher BA, Kerbel RS. Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci USA 1993, 90:3294-8. 10.1073/pnas.90.8.3294, 46286, 8475071.
51. Jain RK. Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. J Natl Cancer Inst 1989, 81:570-6. 10.1093/jnci/81.8.570, 2649688.
52. Bindra RS, Schaffer PJ, Meng A, Woo J, Måseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, Glazer PM. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol 2004, 24:8504-18. 10.1128/MCB.24.19.8504-8518.2004, 516750, 15367671.
53. Plumb JA, Strathdee G, Sludden J, Kaye SB, Brown R. Reversal of drug resistance in human tumor xenografts by 2V-deoxy-5-azacytidineinduced demethylation of the hMLH1 gene promoter. Cancer Res 2000, 60:6039-44.
54. Chan AT, Tao Q, Robertson KD, Flinn IW, Mann RB, Klencke B, Kwan WH, Leung TW, Johnson PJ, Ambinder RF. Azacitidine induces demethylation of the Epstein-Barr virus genome in tumors. J Clin Oncol 2004, 22:1373-81. 10.1200/JCO.2004.04.185, 15007085.
55. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG. Inactivation of the DNArepair geneO6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 1999, 59:793-797.
56. Esteller M, Herman JG. Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer. Oncogene 2004, 23:1-8. 10.1038/sj.onc.1207316, 14712205.
57. Hermann A, Gowher H, Jeltsch A. Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci 2004, 61:2571-2587. 10.1007/s00018-004-4201-1, 15526163.
58. Bae SI, Lee HS, Kim SH, Kim WH. Inactivation of O6-methylguanine-DNA methyltransferase by promoter CpG island hypermethylation in gastric cancers. Br J Cancer 2002, 86:1888-1892. 10.1038/sj.bjc.6600372, 2375420, 12085181.
59. Danam RP, Howell SR, Brent TP, Harris LC. Epigenetic regulation ofO6-methylguanine-DNA methyltransferase gene expression by histone acetylation and methyl-CpG binding proteins. Mol Cancer Ther 2005, 4:1-69.
60. Wang W, Huper G, Guo Y, Murphy SK, Olson JA, Marks JR. Analysis of methylation sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer. Oncogene 2005, 24:705-2714.
61. Michel B, Flores MJ, Viguera E, Grompone G, Seigneur M, Bidnenko V. Rescue of arrested replication forks by homologous recombination. Proc Natl Acad Sci USA 2001, 98:8181-8. 10.1073/pnas.111008798, 37419, 11459951.
62. McGlynn P, Lloyd RG. Recombinational repair and restart of damaged replication forks. Nat Rev Mol Cell Biol 2002, 3:859-70. 10.1038/nrm951, 12415303.
63. Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW. The doublestrand-break repair model for recombination. Cell 1983, 33:25-35. 10.1016/0092-8674(83)90331-8, 6380756.
64. Fishman-Lobell J, Rudin N, Haber JE. Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated. Mol Cell Biol 1992, 12:1292-303. 369562, 1545810.
65. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001, 276:42462-7. 10.1074/jbc.C100466200, 11571274.
66. Rothkamm K, Kruger I, Thompson LH, Lobrich M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 2003, 23:5706-15. 10.1128/MCB.23.16.5706-5715.2003, 166351, 12897142.
67. Durocher D, Jackson SP. DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?. Curr Opin Cell Biol 2001, 13:225-31. 10.1016/S0955-0674(00)00201-5, 11248557.
68. Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med 2006, 12:440-50. 10.1016/j.molmed.2006.07.007, 16899408.
69. Kurz EU, Douglas P, Lees-Miller SP. Doxorubicin activates ATM dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. J Biol Chem 2004, 279:53272-81. 10.1074/jbc.M406879200, 15489221.
70. Kiziltepe T, Hideshima T, Catley L, Raje N, Yasui H. 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicine and bortezomib against multiple myeloma cells. Mol Cancer Ther 2007, 6:1718-1727. 10.1158/1535-7163.MCT-07-0010, 17575103.
71. Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene 2001, 20:1803-15. 10.1038/sj.onc.1204252, 11313928.
72. Wichmann A, Jaklevic B, Su TT. Ionizing radiation induces caspase dependent but Chk2- and p53-independent cell death in Drosophila melanogaster. Proc Natl Acad Sci USA 2006, 103:9952. 10.1073/pnas.0510528103, 1502560, 16785441.
73. Aliouat-Denis CM, Dendouga N, Van den Wyngaert I, Goehlmann H, Steller U, van de Weyer I, Van Slycken N, Andries L, Kass S, Luyten W, Janicot M, Vialard JE. p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2. Mol Cancer Res 2005, 3:627-34. 10.1158/1541-7786.MCR-05-0121, 16317088.
74. Pepper CJ, Hambly RM, Fegan CD, Delavault P, Thurston DE. The novel sequence-specific DNA cross-linking agent SJG-136 (NSC 694501) has potent and selective in vitro cytotoxicity in human B-cell chronic lymphocytic leukemia cells with evidence of a p53-independent mechanism of cell kill. Cancer Res 2004, 64:6750-5. 10.1158/0008-5472.CAN-04-1713, 15374993.
75. Tse AN, Schwartz GK. Potentiation of cytotoxicity of topoisomerase in poison by concurrent and sequential treatment with the checkpoint inhibitor UCN-01 involves disparate mechanisms resulting in either p53-independent clonogenic suppression or p53-dependent mitotic catastrophe. Cancer Res 2004, 64:6635-44. 10.1158/0008-5472.CAN-04-0841, 15374978.
76. Chai G, Li L, Zhou W, Wu L, Zhao Y, Wang D, Lu S, Yu Y, Wang H, McNutt MA, Hu Y, Chen Y, Yang Y, Wu X, Otterson GA, Zhu W. HDAC Inhibitors Act with 5-aza-2'-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells. PLoS One 2008, 3:,3412-20.
77. Nebbioso A, Clarke N, Voltz E, Germain E, Ambrosino C, Bontempo P, Alvarez R, Schiavone EM, Ferrara F, Bresciani F, Weisz A, de Lera AR, Gronemeyer H, Altucci L. Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat Med 2005, 11:77-84. 10.1038/nm1161, 15619633.
78. Xu J, Zhou JY, Tainsky MA, Wu GS. Evidence that Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Induction by 5-Aza-2¶-Deoxycytidine Sensitizes Human Breast Cancer Cells to Adriamycin. Cancer Res 2007, 67:1203-1211. 10.1158/0008-5472.CAN-06-2310, 17283156.
79. Wang Q, Wang X, Hernandez A, Hellmich MR, Gatalica Z, Evers BM. Regulation of TRAIL expression by the phosphatidylinositol 3-kinase/Akt/GSK-3 pathway in human colon cancer cells. J Biol Chem 2002, 277:36602-10. 10.1074/jbc.M206306200, 12140294.
80. Fulda S, Kufer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B, Debatin KM. Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 2001, 20:5865-77. 10.1038/sj.onc.1204750, 11593392.
81. Fulda S, Debatin KM. 5-Aza-2¶-deoxycytidine and IFN-gamma cooperate to sensitize for TRAIL-inducedapoptosis by upregulating caspase-8. Oncogene 2006, 25:5125-33. 10.1038/sj.onc.1209608, 16607283.
82. Gomyo Y, Sasaki J, Branch C, Roth JA, Mukhopadhyay T. 5-aza-2¶-deoxycytidine upregulates caspase-9 expression cooperating with p53-induced apoptosis in human lung cancer cells. Oncogene 2004, 23:6779-87. 10.1038/sj.onc.1207381, 15273730.
83. Nottoli T, Hagopian-Donaldson S, Zhang J, Perkins A, Williams T. AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice. Proc Natl Acad Sci USA 1998, 95:13714-9. 10.1073/pnas.95.23.13714, 24885, 9811866.
84. Feng W, Williams T. Cloning and characterization of the mouse AP-2e gene: a novel family member expressed in the developing olfactory bulb. Mol Cell Neurosci 2003, 24:460-75. 10.1016/S1044-7431(03)00209-4, 14572467.
85. Higler-Eversheim K, Moser M, Schorle H, Buettner R. Regulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell cycle control. Gene 2000, 260:1-12. 10.1016/S0378-1119(00)00454-6, 11137286.
86. McPherson LA, Loktev AV, Weigel RJ. Tumor suppressor activity of AP2a mediated through a direct interaction with p53. J Biol Chem 2002, 277:45028-33. 10.1074/jbc.M208924200, 12226108.
87. Zeng YX, Somasundaram K, El-Deiry WS. AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression. Nat Genet 1997, 15:28-32.
88. Wajapeyee N, Somasundaram K. Cell cycle arrest and apoptosis induction by activator protein 2a (AP-2a) and the role of p53 and p21WAF1/CIP1 in AP-2amediated growth inhibition. J Biol Chem 2003, 278:52093-101. 10.1074/jbc.M305624200, 14551210.
89. Zhang J, Brewer S, Huang J, Williams T. Overexpression of transcription factor AP-2a suppresses mammary gland growth and morphogenesis. Dev Biol 2003, 256:127-45. 10.1016/S0012-1606(02)00119-7, 12654297.
90. Douglas DB, Akiyama Y, Carraway H. Hypermethylation of a small CpGuanine rich region correlates with loss of activator protein-2a expression during progression of breast cancer. Cancer Res 2004, 64:1611-20. 10.1158/0008-5472.CAN-0318-2, 14996719.
91. Anttila MA, Kellokoski JK, Moisio KI, Mitchell PJ, Saarikoski S, Syrjänen K, Kosma VM. Expression of transcription factor AP-2a predicts survival in epithelial ovarian cancer. Br J Cancer 2000, 82:1974-83. 10.1054/bjoc.2000.1146, 2363243, 10864206.
92. Ropponen KM, Kellokoski JK, Pirinen RT, Moisio KI, Eskelinen MJ, Alhava EM, Kosma VM. Expression of transcription factor AP-2 in colorectal adenomas and adenocarcinomas; comparison of immunohistochemistry and in situ hybridisation. J Clin Pathol 2001, 54:533-8. 10.1136/jcp.54.7.533, 1731475, 11429425.
93. Heimberger AB, McGary EC, Suki D, Ruiz M, Wang H, Fuller GN, Bar-Eli M. Loss of the AP-2a transcription factor is associated with the gradeof human gliomas. Clin Cancer Res 2005, 11:267-72. 10.1158/1078-0432.CCR-04-1737, 15671555.
94. Ruiz M, Pettaway C, Song R, Stoeltzing O, Ellis L, Bar-Eli M. Activator protein 2a inhibits tumorigenicity and represses vascular endothelial growth factortranscription in prostate cancer cells. Cancer Res 2004, 64:631-8. 10.1158/0008-5472.CAN-03-2751, 14744778.
95. Gershenwald JE, Sumner W, Calderone T, Wang Z, Huang S, Bar-Eli M. Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growthin vivo. Oncogene 2001, 20:3363-75. 10.1038/sj.onc.1204450, 11423987.
96. Dicato M, Duhem C, Pauly M, Ries F. Multidrug resistance: molecular and clinical aspects. Cytokines Cell Mol Ther 1997, 3:91-9.
97. Hunt CR, Sim JE, Sullivan SJ, Featherstone T, Golden W, Von Kapp-Herr C, Hock RA, Gomez RA, Parsian AJ, Spitz DR. Genomic instability and catalase gene amplification induced by chronic exposure to oxidative stress. Cancer Res 1998, 58:3986-92.
98. Bergelson S, Pinkus R, Daniel V. Intracellular glutathione levels regulate Fos/Jun induction and activation of glutathione S-transferase gene expression. Cancer Res 1994, 54:36-40.
99. Dewey WC. Arrhenius relationships from the molecule and cell to the clinic. Int J Hyperthermia 1994, 10:457-83. 10.3109/02656739409009351, 7963805.
100. Diamond DA, Parsian A, Hunt CR, Lofgren S, Spitz DR, Goswami PC, Gius D. Redox factor-1 (Ref-1) mediates the activation of AP-1 in HeLa and NIH 3T3 cells in response to heat shock. J Biol Chem 1999, 274:16959-64. 10.1074/jbc.274.24.16959, 10358044.
101. Kerppola T, Curran T. Transcription. Zen and the art of Fos and Jun. Nature 1995, 373:199-200. 10.1038/373199a0, 7816132.
102. Martins NM, Santos NA, Curti C, Bianchi ML, Santos AC. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol 2007, 23:234-244.
103. Simons AL, Ahmad IM, Mattson DM, Dornfeld KJ. Spitz DR. 2-Deoxy-Dglucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells. Cancer Res 2007, 67:3364-70. 10.1158/0008-5472.CAN-06-3717, 17409446.
104. Siitonen T, Alaruikka P, Mantymaa P, Savolainen ER, Kavanagh TJ, Krejsa CM, Franklin CC, Kinnula V, Koistinen P. Protection of acute myeloblastic leukemia cells against apoptotic cell death by high glutathione and gammaglutamylcysteine synthetase levels during etoposide-induced oxidative stress. Ann Oncol 1999, 10:1361-7. 10.1023/A:1008382912096, 10631466.
105. Mairesse N, Bernaert D, Del Bino G, Horman S, Mosselmans R, Robaye B, Galand P. Expression of HSP27 results in increased sensitivity to tumor necrosis factor, etoposide, and H2O2 in an oxidative stress-resistant cell line. J Cell Physiol 1998, 177:606-17. 10.1002/(SICI)1097-4652(199812)177:4<606::AID-JCP11>3.0.CO;2-Z, 10092213.
106. Furuta Y, Hunter N, Barkley T, Hall E, Milas L. Increase in radioresponse of murine tumors by treatment with indomethacin. Cancer Res 1988, 48:3008-13.
107. Iliakis G, Seaner R, Okayasu R. Effects of hyperthermia on the repair of radiation-induced DNA single- and double-strand breaks in DNA double-strand break repair-deficient and repair-proficient cell lines. Int J Hyperthermia 1990, 6:813-33. 10.3109/02656739009140828, 2394929.
108. Jurivich DA, Pachetti C, Qiu L, Welk JF. Salicylate triggers heat shock factor differently than heat. J Biol Chem 1995, 270:24489-95. 10.1074/jbc.270.41.24489, 7592665.
109. Jurivich DA, Sistonen L, Kroes RA, Morimoto RI. Effect of sodium salicylate on the human heat shock response. Science 1992, 255:1243-5. 10.1126/science.1546322, 1546322.
110. Bhushan A, Abramson R, Chiu JF, Tritton TR. Expression of c-fos in human and murine multidrug-resistant cells. Mol Pharmacol 1992, 42:69-74.
111. Dignam JD. Preparation of extracts from higher eukaryotes. Methods Enzymol 1990, 182:194-203. full_text, 2314237.
112. Maity A, Kao GD, Muschel RJ, McKenna WG. Potential molecular targets for manipulating the radiation response. Int J Radiat Oncol Biol Phys 1997, 37:639-53. 10.1016/S0360-3016(96)00598-6, 9112463.
113. Yao KS, Godwin AK, Johnson SW, Ozols RF, O'Dwyer PJ, Hamilton TC. Evidence for altered regulation of gamma-glutamylcysteine synthetase gene expression among cisplatin-sensitive and cisplatin-resistant human ovarian cancer cell lines. Cancer Res 1995, 55:4367-74.
114. Bradbury CM, Locke JE, Wei SJ, Shah S, Rene LM, Clemens RA, Roti Roti J, Horikoshi N, Gius D. Increased activator protein 1 activity as well as resistance to heat-induced radiosensitization, hydrogen peroxide, and cisplatin are inhibited by indomethacin in oxidative stress-resistant cells. Cancer Res 2001, 61:3486-92.
115. Mishra MV, Bisht K S, Sun L, Muldoon-Jacobs K, Awwad R, Kaushal A, Nguyen P, Huang L, Pennington JD, Markovina S, Bradbury CM, Gius D. DNMT1 as a Molecular Target in a Multimodality-Resistant Phenotype in Tumor Cells. Mol Cancer Res 2008, 6:243-249. 10.1158/1541-7786.MCR-07-0373, 18314485.
116. Qiu H, Yashiro M, Shinto O, Matsuzaki T, Hirakawa K. DNA methyltransferase inhibitor 5-aza-CdR enhances the radiosensitivity of gastric cancer cells. Cancer Sci 2009, 1:181-188.
117. 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. 10.1073/pnas.81.22.6993, 392062, 6209710.
118. Friedman S. The irreversible binding of azacytosine-containing DNA fragments to bacterial DNA(cytosine-5)methyltransferases. J Biol Chem 1985, 260:5698-705.
119. Gabbara S, Bhagwat AS. The mechanism of inhibition of DNA (cytosine-5-)-methyltransferases by 5-azacytosine is likely to involve methyl transfer to the inhibitor. Biochem J 1995, 307:87-92. 1136748, 7536414.
120. Friedman S, Som S. Induction of EcoRII methyltransferase: evidence for autogenous control. J Bacteriol 1993, 175:6293-8. 206726, 7691793.
121. Liu K, Wang YF, Cantemir C, Muller MT. Endogenous assays of DNA methyltransferases: evidence for differential activities of DNMT1, DNMT2, and DNMT3 in mammalian cells in vivo. Mol Cell Biol 2003, 23:2709-19. 10.1128/MCB.23.8.2709-2719.2003, 152572, 12665573.
122. Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2deoxycytidine 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. 10.1073/pnas.91.25.11797, 45322, 7527544.
123. Ferguson AT, Vertino PM, Spitzner JR, Baylin SB, Muller MT, Davidson NE. Role of estrogen receptor gene demethylation and DNA methyltransferase DNA adduct formation in 5-aza-2¶-deoxycytidine-induced cytotoxicity in human breast cancer cells. J Biol Chem 1997, 272:32260-6. 10.1074/jbc.272.51.32260, 9405430.
124. Karpf AR, Moore BC, Ririe TO, Jones DA. Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2-deoxycytidine. Mol Pharmacol 2001, 59:751-7.
125. 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. 10.1038/sj.onc.1205699, 12154409.
126. Barbe J, Gibert I, Guerrero R. 5-azacytidine: survival and induction of the SOS response in Escherichia coli K-12. Mutat Res 1986, 166:9-16.
127. Lal D, Som S, Friedman S. Survival and mutagenic effects of 5-azacytidine in Escherichia coli. Mutat Res 1988, 193:229-36.
128. Donninger H, Vos MD, Clark GJ. The RASSF1A tumor suppressor. J Cell Sci 2007, 120:3163-72. 10.1242/jcs.010389, 17878233.
129. Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet 2000, 25:315-19. 10.1038/77083, 10888881.
130. Schildhaus HU, Krockel I, Lippert H, Malfertheiner P, Roessner A, Schneider-Stock R. Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach. Int J Oncol 2005, 26:1493-500.
131. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Gnarra JR, Linehan WM. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 1994, 91:9700-9704. 10.1073/pnas.91.21.9700, 44884, 7937876.
132. Alleman WG, Tabios RL, Chandramouli GV, Aprelikova ON, Torres-Cabala C, Mendoza A, Rogers C, Sopko NA, Linehan WM, Vasselli JR. The in vitro and in vivo effects of reexpressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-20-deoxycytidine. Clin Cancer Res 2004, 10:7011-7021. 10.1158/1078-0432.CCR-04-0516, 15501981.
133. Li Q, Ahuja N, Burger PC, Issa JP. Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 1999, 18:3284-3289. 10.1038/sj.onc.1202663, 10359534.
134. Kissil JL, Feinstein E, Cohen O, Jones PA, Tsai YC, Knowles MA, Eydmann ME, Kimchi A. DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: possible implications for role as tumor suppressor gene. Oncogene 1997, 15:403-407. 10.1038/sj.onc.1201172, 9242376.
135. Katzenellenbogen RA, Baylin SB, Herman JG. Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood 1999, 93:4347-4353.
136. Tang X, Sun SY, Wistuba II, Hong WK, Mao L. Hypermethylation of the deathassociated protein kinase promoter attenuates the sensitivity to TRAIL-induced apoptosis in human non-small cell lung cancer cells. Mol Cancer Res 2004, 2:685-691.
137. Reu FJ, Bae SI, Cherkassky L, Leaman DW, Lindner D, Beaulieu N, MacLeod AR, Borden EC. Overcoming resistance to interferon-induced apoptosis of renal carcinoma and melanoma cells by DNA demethylation. J Clin Oncol 2006, 24:3771-3779. 10.1200/JCO.2005.03.4074, 16801630.
138. Reu FJ, Leaman DW, Maitra RR, Bae SI, Cherkassky L, Fox MW, Rempinski DR, Beaulieu N, MacLeod AR, Borden EC. Expression of RASSF1A, an epigenetically silenced tumor suppressor, overcomes resistance to apoptosis induction by interferons. Cancer Res 2006, 66:2785-2793. 10.1158/0008-5472.CAN-05-2303, 1769551, 16510600.
139. Hopkins-Donaldson S, Bodmer JL, Bourloud KB, Brognara CB, Tschopp J, Gross N. Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res 2000, 60:4315-4319.
140. Fulda S, Kufer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B, Debatin KM. Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 2001, 20:5865-5877. 10.1038/sj.onc.1204750, 11593392.
141. Eramo A, Pallini R, Lotti F, Sette G, Patti M, Bartucci M, Ricci-Vitiani L, Signore M, Stassi G, Larocca LM, Crino L, Peschle C, De Maria R. Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand mediated destruction. Cancer Res 2005, 65:11469-11477. 10.1158/0008-5472.CAN-05-1724, 16357155.
142. Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein NF-kappa B by a posttranslational mechanism. Cell 1986, 47:921-928. 10.1016/0092-8674(86)90807-X, 3096580.
143. Criswell T, Leskov K, Miyamoto S, Luo G, Boothman DA. Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene 2003, 22:5813-5827. 10.1038/sj.onc.1206680, 12947388.
144. Jung M, Dritschilo A. NF-kappa B signaling pathway as a target for human tumor radiosensitization. Semin Radiat Oncol 2001, 11:346-351. 10.1053/srao.2001.26034, 11677659.
145. Orlowski RZ, Baldwin AS. NF-kappaB as a therapeutic target in cancer. Trends Mol Med 2002, 8:385-389. 10.1016/S1471-4914(02)02375-4, 12127724.
146. Khong T, Sharkey J, Spencer A. The effect of azacitidine on interleukin-6 signaling and nuclear factor-kB activation and its in vitro and in vivo activity against multiple myeloma. Haematologica 2008, 93:860-869. 10.3324/haematol.12261, 18443271.
147. Sharkey J, Khong T, Spencer A. PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells. Blood 2006, 109:1712-9. 10.1182/blood-2006-05-014092, 17032922.
148. Mitsiades N, Mitsiades CS, Richardson PG, Poulaki V, Tai YT, Chauhan D, Fanourakis G, Gu X, Bailey C, Joseph M, Libermann TA, Schlossman R, Munshi NC, Hideshima T, Anderson KC. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 2003, 101:2377-80. 10.1182/blood-2002-06-1768, 12424198.
149. Martin-Oliva D, Aguilar-Quesada R, O'valle F, Munoz-Gamez JA, Martinez-Romero R, Garcia Del Moral R, Ruiz de Almodóvar JM, Villuendas R, Piris MA, Oliver FJ. Inhibition of poly(ADP-ribose) polymerase modulates tumor-related gene expression, including hypoxia-inducible factor-1 activation, during skin carcinogenesis. Cancer Res 2006, 66:5744-5756. 10.1158/0008-5472.CAN-05-3050, 16740713.
150. Vo QN, Kim WJ, Cvitanovic L. The ATM gene is target for epigenetic silencing in locally advanced breast cancer. Oncogene 2004, 23:9432-9437. 10.1038/sj.onc.1208092, 15516988.
151. Kim WJ, Vo QN, Shrivastav M, Lataxes TA, Brown KD. Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene 2002, 21:3864-3871. 10.1038/sj.onc.1205485, 12032824.
152. Das P. Singal R DNA methylation and cancer. J Clin Oncol 2004, 22:4632-4642. 10.1200/JCO.2004.07.151, 15542813.
153. Dunn BK. Hypomethylation: one side of a larger picture. Ann N Y Acad Sci 2003, 983:28-42. 10.1111/j.1749-6632.2003.tb05960.x, 12724210.
154. Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene 2002, 21:5400-5413. 10.1038/sj.onc.1205651, 12154403.
155. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J. Induction of tumors in mice by genomic hypomethylation. Science 2003, 30:0:489-492.
156. Nishigaki M, Aoyagi K, Danjoh I, Fukaya M, Yanagihara K. Discovery of aberrant expression of R-RAS by cancer-linked DNAhypomethylation in gastric cancer using microarrays. Cancer Res 2005, 65:2115-2124. 10.1158/0008-5472.CAN-04-3340, 15781621.
157. Lutz W, Leon J, Eilers M. Contributions of Myc to tumorigenesis. Biochimica et Biophysica Acta (BBA) 2002, 1602(1):61-71.
158. Wang J, Whang H, Li Z, Wu Q. c-Myc is required for maintenance of glioma cancer stem cells. PLoS ONE 2008, 3:e3769. 10.1371/journal.pone.0003769, 2582454, 19020659.
159. Jupin P, Heber AO, Littelwood T, Evan G. c-Myc-induced sensitization to apoptosis is mediated through cytocrome c release. Genes Dev 1999, 13:1367-1381. 10.1101/gad.13.11.1367, 316765, 10364155.
160. Bucci B, D'Agnano I, Amendola D, Citti A. Myc down-regulation sensitizes melanoma cells to radiotherapy by inhibiting MLH1 and MSH2 mismatch repair proteins. Clin Cancer Res 2005, 11(7):2756-2767. 10.1158/1078-0432.CCR-04-1582, 15814658.
161. Fang JY, Yang L, Zhu HY, Chen YX, Lu J, Lu R. 5-Aza-2'-deoxycitidine indices demethylation and up-regulates transcription of p16INK4A gene in human gastric cancer cell lines. Chin Med J (Engl) 2009, 117(1):99-103.
162. Heller G, Schmidt WM, Ziegler B, Holzer S, Mullauer L. Genome-wide transcriptional response to 5-Aza-2'-deoxycitdine and tricostatin A in multiple myeloma cells. Cancer Res 2008, 68(1):44-54. 10.1158/0008-5472.CAN-07-2531, 18172295.
163. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science 2003, 300:455. 10.1126/science.1083557, 12702868.
164. Yang AS, Estecio MR, Garcia-Manero G, Kantarjian HM, Issa JP. Comment on "Chromosomal instability and tumors promoted by DNA hypomethylation" and "Induction of tumors in mice by genomic hypomethylation". Science 2003, 302:1153. 10.1126/science.1089523, 14615517.
165. Http://www.vidaza.com/patient/default.aspx
166. Dagon® (decitabine for injection). , http://www.supergen.com/
167. Cheng JC, Yoo CB, Weisenberger DJ, Chuang J, Wozniak C, Liang G, Marquez VE, Greer S, Orntoft TF, Thykjaer T, Jones PA. Preferential response of cancer cells to zebularine. Cancer Cell 2004, 6:151-158. 10.1016/j.ccr.2004.06.023, 15324698.
168. Karpf AR, Peterson PW, Rawlins JT, Dalley BK. Inhibition of DNA methyltransferase stimulates the expression of signal transduction and activator transcription 1,2 and 3 genes in colon tumor cells. Proc Natl Acad Sci 1999, 96:14007-1412. 10.1073/pnas.96.24.14007, 24181, 10570189.
169. Karpf AR, Lasek AW, Ririe TO, Hanks AN. Limited gene activation in tumor and normal epithelial cells treated with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine. Molecular Parmacology 2004, 65:18-27.
170. Motegi K, Azuma M, Tamatani T, Ashida Y, Sato M. Expression of aquaporin-5 and fluid secretion from immortalized human salivary gland cells by treatment with 5-Aza2'-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjogren syndrome. Lab Investigation 2005, 85:342-353.
171. Benyon RC, Arthur MJ. Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 2001, 21:373-384. 10.1055/s-2001-17552, 11586466.
172. Hazra S, Xiong S, Wang J. Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells. J Biol Chem 2004, 27(9):11392-11401.
173. Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA. Regulation of myofibroblast transdifferentiation by DNA methylation and MePC2: implication for wound healing and fribrinogenesis. Cell Death and Differentiation 2007, 14:275-285. 10.1038/sj.cdd.4401979, 16763620.
174. Liberto M, Cobrinik D. Growth factor-dependent induction of p21CIP1 by the green tea polyphenol, epigallocatechin gallate. Cancer Lett 2000, 154:151-161. 10.1016/S0304-3835(00)00378-5, 10806303.
175. Sang S, Hou Z, Lambert JD, Yang CS. Redox Properties of Tea Polyphenols and Related Biological Activities. Antioxidants & Redox Signaling 2005, 7:1704-1714.
176. Lambert JD, Sang S, Yang CS. Possible Controversy over Dietary Polyphenols: Benefits vs Risks. Chem Res Toxicol 2007, 20:583-585. 10.1021/tx7000515, 17362033.
177. Sang S, Lambert JD, Hong J, Tian S, Lee MJ, Stark RE, Ho CT, Yang CS. Synthesis and Structure Identification of Thiol Conjugates of (-)-Epigallocatechin Gallate and Their Urinary Levels in Mice. Chem Res Toxicol 2005, 18:1762-176. 10.1021/tx050151l, 16300386.
178. Sang S, Hou Z, Lambert JD, Yang CS. Redox Properties of Tea Polyphenols and Related Biological Activities. Antioxidants & Redox Signaling 2005, 7:1704-1714.
179. Isbrucker RA, Edwards JA, Wolz E, Davidovich A, Bausch J. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. Food Chem Toxicol 2006, 44:636-650. 10.1016/j.fct.2005.11.003, 16387402.
180. Yamamoto T, Hsu S, Lewis J, Wataha J. Green Tea Polyphenol Causes Differential Oxidative Environments in Tumor versus Normal Epithelial Cells. Journal of Pharmacology and Experimental therapeutics 2003, 307:230-237. 10.1124/jpet.103.054676, 12954803.
181. Yang CS, Lee MJ, Chen L. Human salivary tea catechin levels and catechin esterase activities: implication in human cancer prevention studies. Cancer Epidemiol Biomarkers Prev 1999, 8:83-89.
182. Yamamoto T, Hsu S, Lewis J, Wataha J. Green Tea Polyphenol Causes Differential Oxidative Environments in Tumor versus Normal Epithelial Cells. Journal of Pharmacology and Experimental therapeutics 2003, 307:230-237. 10.1124/jpet.103.054676, 12954803.
183. Pohlmann P, DiLeone LP, Cancella AI, Caldas AP. Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix. Am J Clin Oncol 2002, 25:496-501. 10.1097/00000421-200210000-00015, 12393992.
184. Tikoo K, Yunus Ali I, Gupta J, Gupta C. 5-Azaytidine prevents Cisplatin induced nephrotoxicity and potentiates anticancer activity of Cisplatin by involving inhibition of metallothionenin, pAKT and DNMT1 expression in chemical induced cancer rats. Toxicology Letters 2009, 191:158-166. 10.1016/j.toxlet.2009.08.018, 19723570.
185. Qui H, Hashimiro M, Shinto O, Matsuzaki T, Hirakawa K. DNA methyltransferase inhibitor 5-Aza-CdR enhances the radiosensitivity of gastric cancer cells. Cancer Sci 2009, 100:181-188. 10.1111/j.1349-7006.2008.01004.x, 19037991.
186. Santi DV, Garret CE, Barr P. On the mechanism of inhibition of DNA cytosine methyltransferase by cytosine anlogs. Cell 1983, 33:9-10. 10.1016/0092-8674(83)90327-6, 6205762.
187. Christman JK. 5-azacytidine and 5-Aza-2'deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene 2002, 21:5483-5495. 10.1038/sj.onc.1205699, 12154409.
188. Karpf AR, Moore BC, Ririe TO, Jones DA. Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-Aza-2'-deoxycytidine. Mol Pharmacol 2001, 59:751-757.
189. Neylon C, Kralicek AV, Hill TM, Dixon NE. Replication termination in Escherichia coli: structure and antihelicase activity of the Tus-Ter complex. Microbiol Mol Biol Rev 2005, 69:501-526. 10.1128/MMBR.69.3.501-526.2005, 1197808, 16148308.
190. Siaglotti L, Fratta E, Coral S, Cortini E, Covre A, Nicolay HY, Anzalone L, Pezzani L, Di Giacomo AM, Fonsatti E, Coalizzi F, Altomonte M, Calbrò L, Maio M. Epigenetic Drugs as Pleiotropic Agents in Cancer Treatment: Biomolecular Aspects and Clinical Applications. J Cell Physiol 2007, 212:330-344. 10.1002/jcp.21066, 17458893.
191. Mund C, Brueckner B, Lyko F. Reactivation of Epigenetically Silenced Genes by DNA Methyltransferase Inhibitors: Basic Concepts and Clinical Applications. Epigenetics 2006, 1:1. 7-13, 10.4161/epi.1.1.2375, 17998808.
192. Griffiths EA, Gore SV. DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes. Semin Hematol 2008, 45(1):23-30. 10.1053/j.seminhematol.2007.11.007, 2234265, 18179966.