Recent advances in the development of polyamine analogues as antitumor agents

Journal of Medicinal Chemistry

Volumn 52, Issue 15, 2009, Pages 4551-4573

  Casero Jr , Robert A ^b   Woster, Patrick M ^a  

^a WAYNE STATE UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; EFLORNITHINE; POLYAMINE DERIVATIVE; SPERMIDINE DERIVATIVE; SPERMINE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; CANCER RESEARCH; DRUG MECHANISM; DRUG RESEARCH; DRUG TARGETING; HUMAN; NONHUMAN; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOGENIC POLYAMINES; BREAST NEOPLASMS; DNA; DRUG DISCOVERY; EFLORNITHINE; ENZYME INHIBITORS; HISTONE DEACETYLASES; HOMEOSTASIS; HUMANS; OXIDOREDUCTASES, N-DEMETHYLATING; POLYAMINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 68549101792     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900187v     Document Type: Review

References (186)

1. Casero, R. A.; Woster, P. M. Terminally alkylated polyamine analogues as chemotherapeutic agents. J. Med. Chem. 2001, 44 (1), 1-26.
2. Porter, C. W.; Sufrin, J. R. Interference with polyamine biosynthesis and/or function by analogs of polyamines or methionine as a potential anticancer chemotherapeutic strategy. Anticancer Res. 1986, 6 (4), 525-542.
3. Mamont, P. S.; Duchesne, M. C.; Grove, J.; Bey, P. Anti-proliferative properties of DL-alpha-difluoromethyl ornithine in cultured cells. A consequence of the irreversible inhibition of ornithine decarboxylase. Biochem. Biophys. Res.Commun. 1978, 81 (1), 58-66.
4. Danzin, C.; Marchal, P.; Casara, P. Irreversible inhibition of rat S-adenosylmethionine decarboxylase by 5′-([(Z)-4-amino-2- butenyl] methylamino)-5′-deoxyadenosine. Biochem. Pharmacol. 1990, 40 (7), 1499-1503.
5. Tang, K. C.; Mariuza, R.; Coward, J. K. Synthesis and evaluation of some stable multisubstrate adducts as specific inhibitors of spermidine synthase. J. Med. Chem. 1981, 24 (11), 1277-1284.
6. Woster, P. M.; Black, A. Y.; Duff, K. J.; Coward, J. K.; Pegg, A. E. Synthesis and biological evaluation of S-adenosyl-1,12-diamino-3-thio-9- azadodecane, a multisubstrate adduct inhibitor of spermine synthase. J. Med. Chem. 1989, 32 (6), 1300-1307.
7. Cullis, P. M.; Green, R. E.; Merson-Davies, L.; Travis, N. G. Chemical highlights of polyamine transport. Biochem. Soc. Trans. 1998, 26 (4), 595-601.
8. Seiler, N.; Delcros, J. G.; Moulinoux, J. P. Polyamine transport in mammalian cells. An update. Int. J. Biochem. Cell Biol. 1996, 28 (8), 843-861.
9. Weeks, R. S.; Vanderwerf, S. M.; Carlson, C. L.; Burns, M. R.; O'Day, C. L.; Cai, F.; Devens, B. H.; Webb, H. K. Novel lysine-spermine conjugate inhibits polyamine transport and inhibits cell growth when given with DFMO. Exp. Cell Res. 2000, 261 (1), 293-302.
10. Bacchi, C. J.; Garofalo, J.; Mockenhaupt, D.; McCann, P. P.; Diekema, K. A.; Pegg, A. E.; Nathan, H. C.; Mullaney, E. A.; Chunosoff, L.; Sjoerdsma, A.; Hutner, S. H. In vivo effects of alpha-DL-difluoromethylornithine on the metabolism and morphology of Trypanosoma brucei brucei. Mol. Biochem. Parasitol. 1983, 7 (3), 209-225.
11. Bacchi, C. J.; Nathan, H. C.; Livingston, T.; Valladares, G.; Saric, M.; Sayer, P. D.; Njogu, A. R.; Clarkson, A. B. Jr. Differential susceptibility to DL-alpha-difluoromethylornithine in clinical isolates of Trypanosoma brucei rhodesiense. Antimicrob. Agents Chemother. 1990, 34 (6), 1183-1188.
12. Wang, X.; Feith, D. J.; Welsh, P.; Coleman, C. S.; Lopez, C.; Woster, P. M.; O'Brien, T. G.; Pegg, A. E. Studies of the mechanism by which increased spermidine/spermine N1-acetyltransferase activity increases susceptibility to skin carcinogenesis. Carcinogenesis 2007, 28 (11), 2404-2411.
13. Meyskens, F. L. Jr.; Gerner, E. W. Development of difluoromethy- lornithine (DFMO) as a chemoprevention agent. Clin. Cancer Res. 1999, 5 (5), 945-951.
14. Raul, F.; Gosse, F.; Osswald, A. B.; Bouhadjar, M.; Foltzer-Jourdainne, C.; Marescaux, J.; Soler, L. Follow-up of tumor development in the colons of living rats and implications for chemoprevention trials: assessment of aspirin-difluoromethylornithine combination. Int. J. Oncol. 2007, 31 (1), 89-95.
15. Bergeron, R. J.; McManis, J. S.; Weimar, W. R.; Schreier, K. M.; Gao, F.; Wu, Q.; Ortiz-Ocasio, J.; Luchetta, G. R.; Porter, C.; Vinson, J. R. The role of charge in polyamine analogue recognition. J. Med. Chem. 1995, 38 (13), 2278-2285.
16. Casero, R. A. Jr.; Marton, L. J. Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat. Rev. Drug Discovery 2007, 6 (5), 373-390.
17. Wallace, H. M.; Niiranen, K. Polyamine analogues, an update. Amino Acids 2007, 33 (2), 261-265.
18. Casero, R. A. Jr.; Frydman, B.; Stewart, T. M.; Woster, P. M. Significance of targeting polyamine metabolism as an antineoplastic strategy: unique targets for polyamine analogues. Proc. West. Pharmacol. Soc. 2005, 48, 24-30.
19. Boncher, T.; Bi, X.; Varghese, S.; Casero, R. A. Jr.; Woster, P. M. Polyamine-based analogues as biochemical probes and potential therapeutics. Biochem. Soc. Trans. 2007, 35 (Part 2), 356-363.
20. Heby, O.; Persson, L.; Rentala, M. Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas' disease, and leishmaniasis. Amino Acids 2007, 33 (2), 359-366.
21. Wallace, H. M. Targeting polyamine metabolism: a viable therapeutic/ preventative solution for cancer. Expert Opin. Pharmacother. 2007, 8 (13), 2109-2116.
22. Gerner, E. W.; Meyskens, F. L. Jr. Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 2004, 4 (10), 781-792.
23. Abeloff, M. D.; Slavik, M.; Luk, G. D.; Griffin, C. A.; Hermann, J.; Blanc, O.; Sjoerdsma, A.; Baylin, S. B. Phase I trial and pharmacokinetic studies of alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis. J. Clin. Oncol. 1984, 2 (2), 124-130.
24. Meyskens, F. L.; Kingsley, E. M.; Glattke, T.; Loescher, L.; Booth, A. A phase II study of alpha-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma. Invest. New Drugs 1986, 4 (3), 257-262.
25. Abeloff, M. D.; Rosen, S. T.; Luk, G. D.; Baylin, S. B.; Zeltzman, M.; Sjoerdsma, A. Phase II trials of alpha-difluoromethyl-ornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. Cancer Treat. Rep. 1986, 70 (7), 843-845.
26. Herr, H. W.; Warrel, R. P.; Burchenal, J. H. Phase I trial of alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanyl-hydrazone) (MGBG) in patients with advanced prostatic cancer. Urology 1986, 28 (6), 508-511.
27. Paulson, Y. J.; Gilman, T. M.; Heseltine, P. N.; Sharma, O. P.; Boylen, C. T. Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Chest 1992, 101 (1), 67-74.
28. Van Nieuwenhove, S.; Schechter, P. J.; Declercq, J.; Bone, G.; Burke, J.; Sjoerdsma, A. Treatment of gambiense sleeping sickness in the Sudan with oral DFMO (DL-alpha-difluoromethylornithine), an inhibitor of ornithine decarboxylase; first field trial. Trans. R. Soc. Trop. Med. Hyg. 1985, 79 (5), 692-698.
29. Bitonti, A. J.; Byers, T. L.; Bush, T. L.; Casara, P. J.; Bacchi, C. J.; Clarkson, A. B. Jr.; McCann, P. P.; Sjoerdsma, A. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of S-adenosyl-methionine decarboxylase. Antimicrob. Agents Chemother. 1990, 34 (8), 1485-1490.
30. Reddy, B. S.; Nayini, J.; Tokumo, K.; Rigotty, J.; Zang, E.; Kelloff, G. Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha- difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. Cancer Res. 1990, 50 (9), 2562-2568.
31. Alberts, D. S.; Dorr, R. T.; Einspahr, J. G.; Aickin, M.; Saboda, K.; Xu, M. J.; Peng, Y. M.; Goldman, R.; Foote, J. A.; Warneke, J. A.; Salasche, S.; Roe, D. J.; Bowden, G. T. Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dlornithine. Cancer Epidemiol., Biomarkers Prev. 2000, 9 (12), 1281-1286.
32. Stratton, S. P.; Dorr, R. T.; Alberts, D. S. The state-of-the-art in chemoprevention of skin cancer. Eur. J. Cancer 2000, 36 (10), 1292-1297.
33. Simoneau, A. R.; Gerner, E. W.; Nagle, R.; Ziogas, A.; Fujikawa-Brooks, S.; Yerushalmi, H.; Ahlering, T. E.; Lieberman, R.; McLaren, C. E.; Anton-Culver, H.; Meyskens, F. L. Jr. The effect of difluoromethylornithine on decreasing prostate size and polyamines in men: results of a year-long phase IIb randomized placebo-controlled chemoprevention trial. Cancer Epidemiol., Biomarkers Prev. 2008, 17 (2), 292-299.
34. Meyskens, F. L. Jr.; McLaren, C. E.; Pelot, D.; Fujikawa-Brooks, S.; Carpenter, P. M.; Hawk, E.; Kelloff, G.; Lawson, M. J.; Kidao, J.; McCracken, J.; Albers, C. G.; Ahnen, D. J.; Turgeon, D. K.; Goldschmid, S.; Lance, P.; Hagedorn, C. H.; Gillen, D. L.; Gerner, E. W. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev. Res. (Philadelphia, PA) 2008, 1 (1), 32-38.
35. McLaren, C. E.; Fujikawa-Brooks, S.; Chen, W. P.; Gillen, D. L.; Pelot, D.; Gerner, E. W.; Meyskens, F. L. Jr. Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. Cancer Prev. Res. (Philadelphia, PA) 2008, 1 (7), 514-521.
36. Zell, J. A.; Pelot, D.; Chen, W. P.; McLaren, C. E.; Gerner, E. W.; Meyskens, F. L. Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer Prev. Res. (Philadelphia, PA) 2009, 2 (3), 209-212.
37. Edwards, M. L.; Prakash, N. J.; Stemerick, D. M.; Sunkara, S. P.; Bitonti, A. J.; Davis, G. F.; Dumont, J. A.; Bey, P. Polyamine analogues with antitumor activity. J. Med. Chem. 1990, 33 (5), 1369-1375.
38. Edwards, M. L.; Snyder, R. D.; Stemerick, D. M. Synthesis and DNA-binding properties of polyamine analogues. J. Med. Chem. 1991, 34 (8), 2414-2420.
39. Porter, C. W.; Berger, F. G.; Pegg, A. E.; Ganis, B.; Bergeron, R. J. Regulation of ornithine decarboxylase activity by spermidine and the spermidine analogue N1N8-bis(ethyl)spermidine. Biochem. J. 1987, 242 (2), 433-440.
40. Porter, C. W.; Ganis, B.; Libby, P. R.; Bergeron, R. J. Correlations between polyamine analogue-induced increases in spermidine/ spermine N1-acetyltransferase activity, polyamine pool depletion, and growth inhibition in human melanoma cell lines. Cancer Res. 1991, 51 (14), 3715-3720.
41. Bergeron, R. J.; Neims, A. H.; McManis, J. S.; Hawthorne, T. R.; Vinson, J. R.; Bortell, R.; Ingeno, M. J. Synthetic polyamine analogues as antineoplastics. J. Med. Chem. 1988, 31 (6), 1183-1190.
42. Bergeron, R. J.; Feng, Y.; Weimar, W.R.; McManis, J. S.; Dimova, H.; Porter, C.; Raisler, B.; Phanstiel, O. A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics. J. Med. Chem. 1997, 40 (10), 1475-1494.
43. Bergeron, R. J.; McManis, J. S.; Liu, C. Z.; Feng, Y.; Weimar, W. R.; Luchetta, G. R.; Wu, Q.; Ortiz-Ocasio, J.; Vinson, J. R.; Kramer, D. Antiproliferative properties of polyamine analogues: a structure-activity study. J. Med. Chem. 1994, 37 (21), 3464-3476.
44. Jeffers, L.; Church, D.; Basu, H.; Marton, L.; Wilding, G. Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the proliferation of three prostate cancer cell lines. Cancer Chemother. Pharmacol. 1997, 40 (2), 172-179.
45. Bergeron, C. J.; Basu, H. S.; Marton, L. J.; Deen, D. F.; Pellarin, M.; Feuerstein, B. G. Two polyamine analogs (BE-4-4-4 and BE-4-4-4-4) directly affect growth, survival, and cell cycle progression in two human brain tumor cell lines. Cancer Chemother. Pharmacol. 1995, 36 (5), 411-417.
46. Roemmele, R. C.; Rappoport, H. Removal of N-arylsulfonyl groups from hydroxy alpha-amino acids. J. Org. Chem. 1988, 53, 2367-2371.
47. Yajima, H.; Takeyama, M.; Kanaki, J.; Nishimura, O.; Fujino, M. Studies on peptides. LXXX. NG-Mesitylene-2-sulfonylarginine. Chem. Pharm. Bull. 1978, 26, 3752-3757.
48. Bergeron, R. J.; Muller, R.; Huang, G.; McManis, J. S.; Algee, S. E.; Yao, H.; Weimar, W. R.; Wiegand, J. Synthesis and evaluation of hydroxylated polyamine analogues as antiproliferatives. J. Med. Chem. 2001, 44 (15), 2451-2459.
49. Bergeron, R. J.; Wiegand, J.; Fannin, T. L. Control of irritable bowel syndrome with polyamine analogs: a structure-activity study. Dig. Dis. Sci. 2001, 46 (12), 2615-2623.
50. Bergeron, R. J.; Wiegand, J.; McManis, J. S.; Weimar, W. R.; Smith, R. E.; Algee, S. E.; Fannin, T. L.; Slusher, M. A.; Snyder, P. S. Polyamine analogue antidiarrheals: a structure-activity study. J. Med. Chem. 2001, 44 (2), 232-244.
51. Wolff, A. C.; Armstrong, D. K.; Fetting, J. H.; Carducci, M. K.; Riley, C. D.; Bender, J. F.; Casero, R. A. Jr.; Davidson, N. E. A phase II study of the polyamine analog N1,N11-diethylnorspermine (DENSpm) daily for five days every 21 days in patients with previously treated metastatic breast cancer. Clin. Cancer Res. 2003, 9 (16, Part 1), 5922-5928.
52. Hahm, H. A.; Ettinger, D. S.; Bowling, K.; Hoker, B.; Chen, T. L.; Zabelina, Y.; Casero, R. A. Jr. Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer. Clin. Cancer Res. 2002, 8 (3), 684-690.
53. Streiff, R. R.; Bender, J. F. Phase 1 study of N1-N11-diethylnorspermine (DENSPM) administered TID for 6 days in patients with advanced malignancies. Invest. New Drugs 2001, 19 (1), 29-39.
54. Hector, S.; Tummala, R.; Kisiel, N. D.; Diegelman, P.; Vujcic, S.; Clark, K.; Fakih, M.; Kramer, D. L.; Porter, C. W.; Pendyala, L. Polyamine catabolism in colorectal cancer cells following treatment with oxaliplatin, 5-fluorouracil and N1,N11 diethylnorspermine. Cancer Chemother. Pharmacol. 2008, 62 (3), 517-527.
55. Bergeron, R. J.; Yao, G. W.; Yao, H.; Weimar, W. R.; Sninsky, C. A.; Raisler, B.; Feng, Y.; Wu, Q.; Gao, F. Metabolically programmed polyamine analogue antidiarrheals. J. Med. Chem. 1996, 39 (13), 2461-2471.
56. Reddy, V. K.; Valasinas, A.; Sarkar, A.; Basu, H. S.; Marton, L. J.; Frydman, B. Conformationally restricted analogues of 1N,12N-bisethylspermine: synthesis and growth inhibitory effects on human tumor cell lines. J. Med. Chem. 1998, 41 (24), 4723-4732.
57. Seiler, N.; Delcros, J. G.; Vaultier, M.; Le Roch, N.; Havouis, R.; Douaud, F.; Moulinoux, J. P. Bis(7-amino-4-azaheptyl)dimethlysilane and bis(7-ethylamino-4-azaheptyl)dimethylsilane: inhibition of tumor cell growth in vitro and in vivo. Cancer Res. 1996, 56 (24), 5624-5630.
58. Waters, W. R.; Frydman, B.; Marton, L. J.; Valasinas, A.; Reddy, V. K.; Harp, J. A.; Wannemuehler, M. J.; Yarlett, N. [(1)N,(12)N] Bis(ethyl) -cis-6,7-dehydrospermine: a new drug for treatment and prevention of Cryptosporidium parvum infection of mice deficient in T-cell receptor alpha. Antimicrob. Agents Chemother. 2000, 4410, 2891-2894.
59. Frydman, B.; Porter, C. W.; Maxuitenko, Y.; Sarkar, A.; Bhattacharya, S.; Valasinas, A.; Reddy, V. K.; Kisiel, N.; Marton, L. J.; Basu, H. S. A novel polyamine analog (SL-11093) inhibits growth of human prostate tumor xenografts in nude mice. Cancer Chemother. Pharmacol. 2003, 51 (6), 488-492.
60. Carew, J. S.; Nawrocki, S. T.; Reddy, V. K.; Bush, D.; Rehg, J. E.; Goodwin, A.; Houghton, J. A.; Casero, R. A. Jr.; Marton, L. J.; Cleveland, J. L. The novel polyamine analogue CGC-11093 enhances the antimyeloma activity of bortezomib. Cancer Res. 2008, 68 (12), 4783-4790.
61. Valasinas, A.; Sarkar, A.; Reddy, V. K.; Marton, L. J.; Basu, H. S.; Frydman, B. Conformationally restricted analogues of 1N,14N-bisethylhomospermine (BE-4-4-4): synthesis and growth inhibitory effects on human prostate cancer cells. J. Med. Chem. 2001, 44 (3), 390-403.
62. Frydman, B.; Blokhin, A. V.; Brummel, S.; Wilding, G.; Maxuitenko, Y.; Sarkar, A.; Bhattacharya, S.; Church, D.; Reddy, V. K.; Kink, J. A.; Marton, L. J.; Valasinas, A.; Basu, H. S. Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice. J. Med. Chem. 2003, 46 (21), 4586-4600.
63. Reddy, V. K.; Sarkar, A.; Valasinas, A.; Marton, L. J.; Basu, H. S.; Frydman, B. Cis-unsaturated analogues of 3,8,13,18,23-pentaaza-pentacosane (BE-4-4-4-4): synthesis and growth inhibitory effects on human prostate cancer cell lines. J. Med. Chem. 2001, 44 (3), 404-417.
64. Hacker, A.; Marton, L. J.; Sobolewski, M.; Casero, R. A. Jr. In vitro and in vivo effects of the conformationally restricted polyamine analogue CGC-11047 on small cell and non-small cell lung cancer cells. Cancer Chemother. Pharmacol. 2008, 63, 45-53.
65. Lima e Silva, R.; Kachi, S.; Akiyama, H.; JiKui, S.; Hatara, M. C.; Aslam, S.; Gong, Y. Y.; Khu, N. H.; Lauer, T. W.; Hackett, S. F.; Marton, L. J.; Campochiaro, P. A. Trans-scleral delivery of polyamine analogs for ocular neovascularization. Exp. Eye Res. 2006, 83 (5), 1260-1267.
66. Valasinas, A.; Reddy, V. K.; Blokhin, A. V.; Basu, H. S.; Bhattacharya, S.; Sarkar, A.; Marton, L. J.; Frydman, B. Long-chain polyamines (oligoamines) exhibit strong cytotoxicities against human prostate cancer cells. Bioorg. Med. Chem. 2003, 11 (18), 4121-4131.
67. Huang, Y.; Hager, E. R.; Phillips, D. L.; Dunn, V. R.; Hacker, A.; Frydman, B.; Kink, J. A.; Valasinas, A. L.; Reddy, V. K.; Marton, L. J.; Casero, R. A. Jr.; Davidson, N. E. A novel polyamine analog inhibits growth and induces apoptosis in human breast cancer cells. Clin. Cancer Res. 2003, 9 (7), 2769-2777.
68. Huang, Y.; Keen, J. C.; Hager, E.; Smith, R.; Hacker, A.; Frydman, B.; Valasinas, A. L.; Reddy, V. K.; Marton, L. J.; Casero, R. A. Jr.; Davidson, N. E. Regulation of polyamine analogue cytotoxicity by c-Jun in human MDA-MB-435 cancer cells. Mol. Cancer Res. 2004, 2 (2), 81-88.
69. Huang, Y.; Keen, J. C.; Pledgie, A.; Marton, L. J.; Zhu, T.; Sukumar, S.; Park, B. H.; Blair, B.; Brenner, K.; Casero, R. A. Jr.; Davidson, N. E. Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells. J. Biol. Chem. 2006, 281 (28), 19055-19063.
70. Feng, X.; Reddy, V. K.; Mayanja-Kizza, H.; Weiss, L. M.; Marton, L. J.; Tzipori, S. Therapeutic evaluation of polyamine analogue drug candidates against Enterocytozoon bieneusi in the SCID mouse model. Antimicrob. Agents Chemother. 2009, doi:10.1128/ AAC.01113-08.
71. Rukunga, G. M.; Waterman, P. G. New macrocyclic spermine (budmunchiamine) alkaloids from Albizia gummifera: with some observations on the structure-activity relationships of the bud-munchiamines. J. Nat. Prod. 1996, 59 (9), 850-853.
72. Frydman, B.; Bhattacharya, S.; Sarkar, A.; Drandarov, K.; Chesnov, S.; Guggisberg, A.; Popaj, K.; Sergeyev, S.; Yurdakul, A.; Hesse, M.; Basu, H. S.; Marton, L. J. Macrocyclic polyamines deplete cellular ATP levels and inhibit cell growth in human prostate cancer cells. J. Med. Chem. 2004, 47 (4), 1051-1059.
73. Creaven, P. J.; Perez, R.; Pendyala, L.; Meropol, N. J.; Loewen, G.; Levine, E.; Berghorn, E.; Raghavan, D. Unusual central nervous system toxicity in a phase I study of N1N11 diethylnorspermine in patients with advanced malignancy. Invest. New Drugs 1997, 15 (3), 227-234.
74. Wilding, G.; King, D.; Tutsch, K.; Pomplun, M.; Feierabend, C.; Alberti, D.; Arzoomanian, R. Phase I trial of the polyamine analog N1,N14- diethylhomospermine (DEHSPM) in patients with advanced solid tumors. Invest. New Drugs 2004, 22 (2), 131-138.
75. Saab, N. H.;West, E. E.; Bieszk,N. C.; Preuss, C. V.; Mank, A. R.; Casero, R. A. Jr.; Woster, P. M. Synthesis and evaluation of unsymmetrically substituted polyamine analogues as modulators of human spermidine/spermine-N1- acetyltransferase (SSAT) and as potential antitumor agents. J. Med. Chem. 1993, 36 (20), 2998-3004.
76. Casero, R. A. Jr.; Celano, P.; Ervin, S. J.; Porter, C. W.; Bergeron, R. J.; Libby, P. R. Differential induction of spermidine/spermine N1-acetyltransferase in human lung cancer cells by the bis(ethyl) polyamine analogues. Cancer Res. 1989, 49 (14), 3829-3833.
77. Casero, R. A. Jr.; Celano, P.; Ervin, S. J.; Wiest, L.; Pegg, A. E. High specific induction of spermidine/spermine N1-acetyltransferase in a human large cell lung carcinoma. Biochem. J. 1990, 270 (3), 615-620.
78. Casero, R. A. Jr.; Ervin, S. J.; Celano, P.; Baylin, S. B.; Bergeron, R. J. Differential response to treatment with the bis(ethyl)polyamine analogues between human small cell lung carcinoma and undifferentiated large cell lung carcinoma in culture. Cancer Res. 1989, 49 (3), 639-643.
79. Davidson, N. E.; Hahm, H. A.; McCloskey, D. E.; Woster, P. M.; Casero, R. A. Jr. Clinical aspects of cell death in breast cancer: the polyamine pathway as a new target for treatment. Endocr.-Relat. Cancer 1999, 6 (1), 69-73.
80. Ha, H. C.; Woster, P. M.; Casero, R. A. Jr. Unsymmetrically substituted polyamine analogue induces caspase-independent programmed cell death in Bcl-2-overexpressing cells. Cancer Res. 1998, 58 (13), 2711-2714.
81. Ha, H. C.; Woster, P. M.; Yager, J. D.; Casero, R. A. Jr. The role of polyamine catabolism in polyamine analogue-induced programmed cell death. Proc. Natl. Acad. Sci. U.S.A. 1997, 94 (21), 11557-11562.
82. Hu, R. H.; Pegg, A. E. Rapid induction of apoptosis by deregulated uptake of polyamine analogues. Biochem. J. 1997, 328 (Part 1), 307-316.
83. McCloskey, D. E.; Casero, R. A. Jr.; Woster, P. M.; Davidson, N. E. Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue. Cancer Res. 1995, 55 (15), 3233-3236.
84. McCloskey, D. E.; Woster, P. M.; Casero, R. A. Jr.; Davidson, N. E. Effects of the polyamine analogues N1-ethyl-N11-((cyclopropyl) methyl)-4,8-diazaundecane and N1-ethylN-11-((cycloheptyl) methyl)-4,8- diazaundecane in human prostate cancer cells. Clin. Cancer Res. 2000, 6 (1), 17-23.
85. McCloskey, D. E.; Yang, J.; Woster, P. M.; Davidson, N. E.; Casero, R. A. Jr. Polyamine analogue induction of programmed cell death in human lung tumor cells. Clin. Cancer Res. 1996, 2 (3), 441-446.
86. Webb, H. K.; Wu, Z.; Sirisoma, N.; Ha, H. C.; Casero, R. A. Jr.; Woster, P. M. 1-(N-alkylamino)-11-(N-ethylamino)-4,8-diazaundecanes: simple synthetic polyamine analogues that differentially alter tubulin polymerization. J. Med. Chem. 1999, 42 (8), 1415-1421.
87. Bellevue, F. H. III; Boahbedason, M.; Wu, R.; Woster, P. M.; Casero, R. A. Jr.; Rattendi, D.; Lane, S.; Bacchi, C. J. Structural comparison of alkylpolyamine analogues with potent in vitro antitumor or antiparasitic activity. Bioorg. Med. Chem. Lett. 1996, 6 (22), 2765.
88. Bi, X.; Lopez, C.; Bacchi, C. J.; Rattendi, D.; Woster, P. M. Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity. Bioorg. Med. Chem. Lett. 2006, 16 (12), 3229-3232.
89. Bergeron, R. J.; Hawthorne, T. R.; Vinson, J. R.; Beck, D. E. Jr.; Ingeno, M. J. Role of the methylene backbone in the antiproliferative activity of polyamine analogues on L1210 cells. Cancer Res. 1989, 49 (11), 2959-2964.
90. Casero, R. A. Jr.; Mank, A. R.; Xiao, L.; Smith, J.; Bergeron, R. J.; Celano, P. Steady-state messenger RNA and activity correlates with sensitivity to N1,N12-bis(ethyl)spermine in human cell lines representing the major forms of lung cancer. Cancer Res. 1992, 52 (19), 5359-5363.
91. Bacchi, C. J.; Yarlett, N.; Faciane, E.; Bi, X.; Rattendi, D.; Weiss, L. M.; Woster, P. M. Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi. Antimicrob. Agents Chemother. 2009, doi:10.1128/ AAC.00267-08.
92. Rosenberg, B.; Vancamp, L.; Krigas, T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 1965, 205, 698-699.
93. Barry, M. A.; Behnke, C. A.; Eastman, A. Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem. Pharmacol. 1990, 40 (10), 2353-2362.
94. Wang, D.; Lippard, S. J. Cellular processing of platinum anticancer drugs. Nat. Rev. Drug Discovery 2005, 4 (4), 307-320.
95. Rabik, C. A.; Dolan, M. E. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat. Rev. 2007, 33 (1), 9-23.
96. Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer 2007, 7 (8), 573-584.
97. Asara, J. M.; Hess, J. S.; Lozada, E.; Dunbar, K. R.; Allison, J. Evidence for binding of dirhodium bis-acetate units to adjacent GG and AA sites on single-stranded DNA. J. Am. Chem. Soc. 2000, 122 (1), 8-13.
98. Catalan, K. V.; Mindiola, D. J.; Ward, D. L.; Dunbar, K. R. A novel dirhodium compound with neutral, bridging 9-ethyladenine ligands. Inorg. Chem. 1997, 36 (11), 2458-2460.
99. Kang, M.; Chifotides, H. T.; Dunbar, K. R. 2DNMRstudy of the DNA duplex d(CTCTC*A*ACTTCC).d(GGAAGTTGAGAG) cross-linked by the antitumor-active dirhodium(II,II) unit at the cytosine-adenine step. Biochemistry 2008, 47 (8), 2265-2276.
100. Kraker, A. J.; Hoeschele, J. D.; Elliott, W. L.; Showalter, H. D.; Sercel, A. D.; Farrell, N. P. Anticancer activity in murine and human tumor cell lines of bis(platinum) complexes incorporating straight-chain aliphatic diamine linker groups. J. Med. Chem. 1992, 35 (24), 4526-4532.
101. Navarro-Ranninger, C.; Ochoa, P. A.; Perez, J. M.; Gonzalez, V. M.; Masaguer, J. R.; Alonso, C. Platinum (II) and (IV) spermidine complexes. Synthesis, characterization, and biological studies. J. Inorg. Biochem. 1994, 53 (3), 177-190.
102. Rauter, H.; DiDomenico, R.; Menta, E.; Oliva, A.; Qu, Y.; Farrell, N. Selective platination of biologically relevant polyamines. Linear coordinating spermidine and spermine as amplifying linkers in dinuclear platinum complexes. Inorg. Chem. 1997, 36 (18), 3919-3927.
103. Amo-Ochoa, P.; Gonzalez, V. M.; Perez, J. M.; Masaguer, J. R.; Alonso, C.; Navarro-Ranninger, C. Cytotoxicity, DNA binding, and reactivity against nucleosides of platinum (II) and (IV) spermine compounds. J. Inorg. Biochem. 1996, 64 (4), 287-299.
104. Di Blasi, P.; Bernareggi, A.; Beggiolin, G.; Piazzoni, L.; Menta, E.; Formento, M. L. Cytotoxicity, cellular uptake and DNA binding of the novel trinuclear platinun complex BBR 3464 in sensitive and cisplatin resistant murine leukemia cells. Anticancer Res. 1998, 18 (4C), 3113-3117.
105. Brabec, V.; Kasparkova, J.; Vrana, O.; Novakova, O.; Cox, J. W.; Qu, Y.; Farrell, N. DNA modifications by a novel bifunctional trinuclear platinum phase I anticancer agent. Biochemistry 1999, 38 (21), 6781-6790.
106. McGregor, T. D.; Hegmans, A.; Kasparkova, J.; Neplechova, K.; Novakova, O.; Penazova, H.; Vrana, O.; Brabec, V.; Farrell, N.A comparison of DNA binding profiles of dinuclear platinum compounds with polyamine linkers and the trinuclear platinum phase II clinical agent BBR3464. J. Biol. Inorg. Chem. 2002, 7 (4-5), 397-404.
107. Billecke, C.; Finniss, S.; Tahash, L.; Miller, C.; Mikkelsen, T.; Farrell, N. P.; Bogler, O. Polynuclear platinum anticancer drugs are more potent than cisplatin and induce cell cycle arrest in glioma. Neuro-Oncology 2006, 8 (3), 215-226.
108. Chvalova, K.; Kasparkova, J.; Farrell, N.; Brabec, V. Deoxyribonuclease I footprinting reveals different DNA binding modes of bifunctional platinum complexes. FEBS J. 2006, 273 (15), 3467-3478.
109. Jodrell, D. I.; Evans, T.R.; Steward, W.; Cameron, D.; Prendiville, J.; Aschele, C.; Noberasco, C.; Lind, M.; Carmichael, J.; Dobbs, N.; Camboni, G.; Gatti, B.; De Braud, F. Phase II studies of BBR3464, a novel tri-nuclear platinum complex, in patients with gastric or gastro-oesophageal adenocarcinoma. Eur. J. Cancer 2004, 40 (12), 1872-1877.
110. Hensing, T. A.; Hanna, N. H.; Gillenwater, H. H.; Gabriella Camboni, M.; Allievi, C.; Socinski, M. A. Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer. Anti-Cancer Drugs 2006, 17 (6), 697-704.
111. Mitchell, C.; Kabolizadeh, P.; Ryan, J.; Roberts, J. D.; Yacoub, A.; Curiel, D. T.; Fisher, P. B.; Hagan, M. P.; Farrell, N. P.; Grant, S.; Dent, P. Low-dose BBR3610 toxicity in colon cancer cells is p53-independent and enhanced by inhibition of epidermal growth factor receptor (ERBB1)-phosphatidyl inositol 3 kinase signaling. Mol. Pharmacol. 2007, 72 (3), 704-714.
112. Hegmans, A.; Qu, Y.; Kelland, L. R.; Roberts, J. D.; Farrell, N. Novel approaches to polynuclear platinum pro-drugs. Selective release of cytotoxic platinum-spermidine species through hydrolytic cleavage of carbamates. Inorg. Chem. 2001, 40 (24), 6108-6114.
113. Hegmans, A.; Kasparkova, J.; Vrana, O.; Kelland, L. R.; Brabec, V.; Farrell, N. P. Amide-based prodrugs of spermidine-bridged dinuclear platinum. Synthesis, DNA binding, and biological activity. J. Med. Chem. 2008, 51 (7), 2254-2260.
114. Pegram, M. D.; Slamon, D. J. Combination therapy with trastuzumab (Herceptin) and cisplatin for chemoresistant metastatic breast cancer: evidence for receptor-enhanced chemosensitivity. Semin. Oncol. 1999, 26 (4. Suppl. 12), 89-95.
115. Pietras, R. J.; Fendly, B. M.; Chazin, V. R.; Pegram, M. D.; Howell, S. B.; Slamon, D. J. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 1994, 9 (7), 1829-1838.
116. Hurley, J.; Doliny, P.; Reis, I.; Silva, O.; Gomez-Fernandez, C.; Velez, P.; Pauletti, G.; Powell, J. E.; Pegram, M. D.; Slamon, D. J. Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J. Clin. Oncol. 2006, 24 (12), 1831-1838.
117. Bhattacharyya, A.; Ear, U. S.; Koller, B. H.; Weichselbaum, R. R.; Bishop, D. K. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J. Biol. Chem. 2000, 275 (31), 23899-23903.
118. Hegardt, C.; Johannsson, O. T.; Oredsson, S. M. Rapid caspasedependent cell death in cultured human breast cancer cells induced by the polyamine analogue N(1),N(11)-diethylnorspermine. Eur. J. Biochem. 2002, 269 (3), 1033-1039.
119. Huang, Y.; Hager, E. R.; Phillips, D. L.; Hacker, A.; Frydman, B.; Valasinas, A. L.; Reddy, V. K.; Marton, L. J.; Casero, R. A.; Davidson, N. E. Conformationally constrained polyamine analogues and oligoamines inhibit growth and induce apoptosis in human breast cancer cells. Proc. Am. Assoc. Cancer Res. 2002, 43, 90.
120. Varghese, S.; Gupta, D.; Baran, T.; Jiemjit, A.; Gore, S. D.; Casero, R. A. Jr.; Woster, P. M. Alkyl-substituted polyamino-hydroxamic acids: a novel class of targeted histone deacetylase inhibitors. J. Med. Chem. 2005, 48 (20), 6350-6365.
121. Zou, Y.; Wu, Z.; Sirisoma, N.; Woster, P. M.; Casero, R. A. Jr.; Weiss, L. M.; Rattendi, D.; Lane, S.; Bacchi, C. J. Novel alkylpolyamine analogues that possess both antitrypanosomal and antimicrosporidial activity. Bioorg. Med. Chem. Lett. 2001, 11 (12), 1613-1617.
122. Marks, P. A.; Richon, V. M.; Breslow, R.; Rifkind, R. A. Histone deacetylase inhibitors as new cancer drugs. Curr. Opin. Oncol. 2001, 13 (6), 477-483.
123. Luger, K.; Mader, A. W.; Richmond, R. K.; Sargent, D. F.; Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 1997, 389 (6648), 251-260.
124. Jenuwein, T.; Allis, C. D. Translating the histone code. Science 2001, 293 (5532), 1074-1080.
125. Herman, J. G.; Baylin, S. B. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 2003, 349 (21), 2042-2054.
126. Robertson, K. D. DNA methylation, methyltransferases, and cancer. Oncogene 2001, 20 (24), 3139-3155.
127. Johnstone, R. W. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat. Rev. Drug Discovery 2002, 1 (4), 287-299.
128. Shogren-Knaak, M.; Ishii, H.; Sun, J.-M.; Pazin, M. J.; Davie, J. R.; Peterson, C. L. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 2006, 311 (5762), 844-847.
129. Marks, P.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K. Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer 2001, 1 (3), 194-202.
130. Shogren-Knaak, M.; Ishii, H.; Sun, J.-M.; Pazin, M. J.; Davie, J. R.; Peterson, C. L. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 2006, 311 (5762), 844-847.
131. Haberland, M.; Montgomery, R. L.; Olson, E. N. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet. 2009, 10 (1), 32-42.
132. Gray, S. G.; Ekstrom, T. J. The human histone deacetylase family. Exp. Cell Res. 2001, 262 (2), 75-83.
133. Taunton, J.; Hassig, C. A.; Schreiber, S. L. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 1996, 272 (5260), 408-411.
134. Grozinger, C. M.; Schreiber, S. L. Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. Chem. Biol. 2002, 9 (1), 3-16.
135. Imai, S.; Armstrong, C. M.; Kaeberlein, M.; Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000, 403 (6771), 795-800.
136. Marmorstein, R.; Roth, S. Y. Histone acetyltransferases: function, structure, and catalysis. Curr. Opin. Genet. Dev. 2001, 11 (2), 155-161.
137. Weinmann, H.; Ottow, E. Recent advances in the medicinal chemistry of histone deacetylase inhibitors. Annu. Rep. Med. Chem. 2004, 39, 185-196.
138. Kouraklis, G.; Theocharis, S. Histone deacetylase inhibitors: a novel target of anticancer therapy (review). Oncol. Rep. 2006, 15 (2), 489-494.
139. Ryan, Q. C.; Headlee, D.; Acharya, M.; Sparreboom, A.; Trepel, J. B.; Ye, J.; Figg, W. D.; Hwang, K.; Chung, E. J.; Murgo, A.; Melillo, G.; Elsayed, Y.; Monga, M.; Kalnitskiy, M.; Zwiebel, J.; Sausville, E. A. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J. Clin. Oncol. 2005, 23 (17), 3912-3922.
140. Hu, E.; Dul, E.; Sung, C.-M.; Chen, Z.; Kirkpatrick, R.; Zhang, G.-F.; Johanson, K.; Liu, R.; Lago, A.; Hofmann, G.; Macarron, R.; De Los Frailes, M.; Perez, P.; Krawiec, J.; Winkler, J.; Jaye, M. Identification of novel isoform-selective inhibitors within class I histone deacetylases. J. Pharmacol. Exp. Ther. 2003, 307 (2), 720-728.
141. Glaser, K. B.; Li, J.; Pease, L. J.; Staver, M. J.; Marcotte, P. A.; Guo, J.; Frey, R. R.; Garland, R. B.; Heyman,H. R.; Wada, C. K. Differential protein acetylation induced by novel histone deacetylase inhibitors. Biochem. Biophys. Res. Commun. 2004, 325 (3), 683.
142. Cameron, E. E.; Bachman, K. E.; Myohanen, S.; Herman, J. G.; Baylin, S. B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 1999, 21 (1), 103-107.
143. Herman, J. G.; Civin, C. I.; Issa, J. P.; Collector, M. I.; Sharkis, S.
144. Herman, J. G.; Jen, J.; Merlo, A.; Baylin, S. B. Hypermethylation- associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res. 1996, 56 (4), 722-727.
145. Corn, P. G.; Smith, B. D.; Ruckdeschel, E. S.; Douglas, D.; Baylin, S. B.; Herman, J. G. E-cadherin expression is silenced by 5′ CpG island methylation in acute leukemia. Clin. Cancer Res. 2000, 6 (11), 4243-4248.
146. Ha, H. C.; Sirisoma, N. S.; Kuppusamy, P.; Zweier, J. L.; Woster, P. M.; Casero, R. A. Jr. The natural polyamine spermine functions directly as a free radical scavenger. Proc. Natl. Acad. Sci. U.S.A. 1998, 95 (19), 11140-11145.
147. Ha, H. C.; Yager, J. D.; Woster, P. A.; Casero, R. A. Jr. Structural specificity of polyamines and polyamine analogues in the protection of DNA from strand breaks induced by reactive oxygen species. Biochem. Biophys. Res. Commun. 1998, 244 (1), 298-303.
148. Varghese, S.; Senanayake, T.; Murray-Stewart, T.; Doering, K.; Fraser, A.; Casero, R. A. Jr.; Woster, P. M. Polyaminohydroxamic acids and polyaminobenzamides as isoform selective histone deacetylase inhibitors. J. Med. Chem. 2008, 51 (8), 2447-2456.
149. Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon, A.; Yoshida, M.; Wang, X. F.; Yao, T. P. HDAC6 is a microtubule-associated deacetylase. Nature 2002, 417 (6887), 455-458.
150. Suzuki, T.; Ando, T.; Tsuchiya, K.; Fukazawa, N.; Saito, A.; Mariko, Y.; Yamashita, T.; Nakanishi, O. Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives. J. Med. Chem. 1999, 42 (15), 3001-3003.
151. Dowling, D. P.; Gantt, S. L.; Gattis, S. G.; Fierke, C. A.; Christianson, D. W. Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry 2008, 47 (51), 13554-13563.
152. Belting, M.; Mani, K.; Jonsson, M.; Cheng, F.; Sandgren, S.; Jonsson, S.; Ding, K.; Delcros, J. G.; Fransson, L. A. Glypican-1 is a vehicle for polyamine uptake in mammalian cells: a pivital role for nitrosothiol-derived nitric oxide. J. Biol. Chem. 2003, 278 (47), 47181-47189.
153. Uemura, T.; Yerushalmi, H. F.; Tsaprailis, G.; Stringer, D. E.; Pastorian, K. E.; Hawel, L. 3rd; Byus, C. V.; Gerner, E. W. Identification and characterization of a diamine exporter in colon epithelial cells. J. Biol. Chem. 2008, 283 (39), 26428-26435.
154. Tabe, Y.; Jin, L.; Contractor, R.; Gold, D.; Ruvolo, P.; Radke, S.; Xu, Y.; Tsutusmi-Ishii, Y.; Miyake, K.; Miyake, N.; Kondo, S.; Ohsaka, A.; Nagaoka, I.; Andreeff, M.; Konopleva, M. Novel role of HDAC inhibitors in AML1/ETO AML cells: activation of apoptosis and phagocytosis through induction of annexin A1. Cell Death Differ. 2007, 14 (8), 1443-1456.
155. Chuthapisith, S.; Bean, B. E.; Cowley, G.; Eremin, J. M.; Samphao, S.; Layfield, R.; Kerr, I. D.; Wiseman, J.; El-Sheemy, M.; Sreenivasan, T.; Eremin, O. Annexins in human breast cancer: possible predictors of pathological response to neoadjuvant chemotherapy. Eur. J. Cancer 2009, 45, 1274-1281.
156. Gowri, P. M.; Yu, J. H.; Shaufl, A.; Sperling,M. A.; Menon, R. K. Recruitment of a repressosome complex at the growth hormone receptor promoter and its potential role in diabetic nephropathy. Mol. Cell. Biol. 2003, 23 (3), 815-825.
157. Miao, F.; Gonzalo, I. G.; Lanting, L.; Natarajan, R. In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions. J. Biol. Chem. 2004, 279 (17), 18091-18097.
158. Gray, S. G.; De Meyts, P. Role of histone and transcription factor acetylation in diabetes pathogenesis. Diabetes Metab. Res. Rev. 2005, 21 (5), 416-433.
159. Lee, H. B.; Noh, H.; Seo, J. Y.; Yu, M. R.; Ha, H. Histone deacetylase inhibitors: a novel class of therapeutic agents in diabetic nephropathy. Kidney Int., Suppl. 2007, No. 106, S61-S66.
160. Susick, L.; Senanayake, T.; Veluthakal, R.; Woster, P. M.; Kowluru, A. A novel histone deacetylase inhibitor prevents IL-1beta-induced metabolic dysfunction in pancreatic beta-cells. J. Cell. Mol. Med. 2008, 10, 1-38.
161. Baylin, S. B.; Ohm, J. E. Epigenetic gene silencing in cancer, a mechanism for early oncogenic pathway addiction. Nat. Rev. Cancer 2006, 6 (2), 107-116.
162. Jones, P. A.; Baylin, S. B. The epigenomics of cancer. Cell 2007, 128 (4), 683-692.
163. Shi, Y.; Lan, F.; Matson, C.; Mulligan, P.; Whetstine, J. R.; Cole, P. A.; Casero, R. A.; Shi, Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004, 119 (7), 941-953.
164. Whetstine, J. R.; Nottke, A.; Lan, F.; Huarte, M.; Smolikov, S.; Chen, Z.; Spooner, E.; Li, E.; Zhang, G.; Colaiacovo, M.; Shi, Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 2006, 125 (3), 467-481.
165. Bannister, A. J.; Kouzarides, T. Reversing histone methylation. Nature 2005, 436 (7054), 1103-1106.
166. Kouzarides, T. Histone methylation in transcriptional control. Curr. Opin. Genet. Dev. 2002, 12 (2), 198-209.
167. Martin, C.; Zhang, Y. The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell Biol. 2005, 6 (11), 838-849.
168. Zhang, Y.; Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 2001, 15 (18), 2343-2360.
169. Schneider, R.; Bannister, A. J.; Kouzarides, T. Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem. Sci. 2002, 27 (8), 396-402.
170. Huarte, M.; Lan, F.; Kim, T.; Vaughn, M. W.; Zaratiegui, M.; Martienssen,R. A.; Buratowski, S.; Shi, Y. The fission yeast JMJ2 reverses histone H3 lysine 4 tri-methylation. J. Biol. Chem. 2007, 282, 21662-21670.
171. Tsukada, Y.; Zhang, Y. Purification of histone demethylases from HeLa cells. Methods 2006, 40 (4), 318-326.
172. Huang, J.; Sengupta, R.; Espejo, A. B.; Lee, M. G.; Dorsey, J. A.; Richter, M.; Opravil, S.; Shiekhattar, R.; Bedford, M. T.; Jenuwein, T.; Berger, S. L. p53 is regulated by the lysine demethylase LSD1. Nature 2007, 449 (7158), 105-108.
173. Liang, G.; Klose, R. J.; Gardner, K. E.; Zhang, Y. Yeast Jhd2p is a histone H3 Lys4 trimethyl demethylase. Nat. Struct. Mol. Biol. 2007, 14 (3), 243-245.
174. Schneider, R.; Bannister, A. J.; Myers, F. A.; Thorne, A. W.; Crane-Robinson, C.; Kouzarides, T. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat. Cell Biol. 2004, 6 (1), 73-77.
175. Lee, M. G.; Wynder, C.; Schmidt, D. M.; McCafferty, D. G.; Shiekhattar, R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem. Biol. 2006, 13 (6), 563-567.
176. Huang, Y.; Greene, E.; Murray Stewart, T.; Goodwin, A. C.; Baylin, S. B.; Woster, P. M.;; Casero, R. A. Jr. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 8023-8028.
177. Stavropoulos, P.; Hoelz, A. Lysine-specific demethylase 1 as a potential therapeutic target. Expert Opin. Ther. Targets 2007, 11 (6), 809-820.
178. Culhane, J. C.; Szewczuk, L. M.; Liu, X.; Da, G.; Marmorstein, R.; Cole, P. A. A mechanism-based inactivator for histone demethylase LSD1. J. Am. Chem. Soc. 2006, 128 (14), 4536-4537.
179. Lee, M. G.; Wynder, C.; Cooch, N.; Shiekhattar, R. An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 2005, 437 (7057), 432-435.
180. Schmidt, D. M.; McCafferty, D. G. trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry 2007, 46 (14), 4408-4416.
181. Cona, A.; Manetti, F.; Leone, R.; Corelli, F.; Tavladoraki, P.; Polticelli, F.; Botta, M. Molecular basis for the binding of competitive inhibitors of maize polyamine oxidase. Biochemistry 2004, 43 (12), 3426-3435.
182. Bianchi, M.; Polticelli, F.; Ascenzi, P.; Botta, M.; Federico, R.; Mariottini, P.; Cona, A. Inhibition of polyamine and spermine oxidases by polyamine analogues. FEBS J. 2006, 273 (6), 1115-1123.
183. Stranska, J.; Sebela, M.; Tarkowski, P.; Rehulka, P.; Chmelik, J.; Popa, I.; Pec, P. Inhibition of plant amine oxidases by a novel series of diamine derivatives. Biochimie 2007, 89 (1), 135-144.
184. McGarvey, K. M.; Fahrner, J. A.; Greene, E.; Martens, J.; Jenuwein, T.; Baylin, S. B. Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. Cancer Res. 2006, 66 (7), 3541-3549.
185. Fahrner, J. A.; Eguchi, S.; Herman, J. G.; Baylin, S. B. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 2002, 62 (24), 7213-7218.
186. Akiyama, Y.; Watkins, N.; Suzuki, H.; Jair, K. W.; van Engeland, M.; Esteller, M.; Sakai, H.; Ren, C. Y.; Yuasa, Y.; Herman, J. G.; Baylin, S. B. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol. Cell. Biol. 2003, 23 (23), 8429-8439.