Development of Polyamine Analogs as Cancer Therapeutic Agents

Oncology Research

Volumn 13, Issue 3, 2002, Pages 123-135

  Thomas, Thresia ^a   Balabhadrapathruni, Srivani ^a   Gallo, Michael A ^a   Thomas, T J ^a,b  

^a ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^b Division of Internal Medicine   (United States)

Author keywords

Anticancer drugs; Bis(ethyl)Polyamines; Polyamine analogs; Polyamines

Indexed keywords

BE 333; BE 343; BE 373; BE 444; BE 4444; MEMBRANE PHOSPHOLIPID; POLYAMINE DERIVATIVE; PUTRESCINE DERIVATIVE; SPERMIDINE DERIVATIVE; SPERMINE DERIVATIVE; ANTINEOPLASTIC AGENT; POLYAMINE;

ABDOMINAL CRAMP; ANIMAL MODEL; APOPTOSIS; ASTHENIA; CANCER CELL; CANCER CHEMOTHERAPY; CANCER GROWTH; CATABOLISM; CELL FUNCTION; CENTRAL NERVOUS SYSTEM DISEASE; CONFORMATIONAL TRANSITION; DIARRHEA; DNA STRUCTURE; DOSE RESPONSE; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; DRUG TOLERABILITY; DRUG UPTAKE; HUMAN; HUMAN CELL; NAUSEA; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; ANIMAL; BRAIN TUMOR; BREAST TUMOR; CELL DIVISION; CHEMISTRY; DRUG EFFECT; FEMALE; LUNG TUMOR; MALE; MAMMAL; MELANOMA; METABOLISM; NEOPLASM; PATHOLOGY; PHYSIOLOGY; PROSTATE TUMOR; TOXICITY TESTING; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL TRANSPORT; BRAIN NEOPLASMS; BREAST NEOPLASMS; CELL DIVISION; DRUG DESIGN; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; MAMMALS; MELANOMA; NEOPLASMS; POLYAMINES; PROSTATIC NEOPLASMS; TOXICITY TESTS;

EID: 0042229373     PISSN: 09650407     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (169)

1. Tabor, C. W.; Tabor, H. Polyamines. Annu. Rev. Biochem. 53:749; 1984.
2. Quemener, V.; Chamaillard, L.; Brachet, P.; Havouis, R.; Moulinoux, J. P. The involvement of polyamines in the malignant proliferative process. The anticancer effect of polyamine deprivation. Ann. Gastroenterol. Hepatol. (Paris) 31:181; 1995.
3. Pegg, A. E. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem. J. 234:249; 1986.
4. Marton, L. J.; Pegg, A. E. Polyamines as targets for therapeutic intervention. Annu. Rev. Pharmacol. Toxicol. 35:55; 1995.
5. Thomas, T.; Thomas, T. J. Polyamines in cell growth and cell death: Molecular mechanisms and therapeutic applications. Cell. Mol. Life Sci. 58:244; 2001.
6. Casero, R. A.; Pegg, A. E. The turning point in polyamine metabolism. FASEB J. 7:653; 1993.
7. Morgan, D. M. Polyamines. An overview. Mol. Biotechnol. 11:229; 1999.
8. Seiler, N. Oxidation of polyamines and brain injury. Neurochem. Res. 25:471; 2000.
9. Murakami, Y.; Matsufuji, S.; Miyazaki, Y.; Hayashi, S. Forced expression of antizyme abolishes ornithine decarboxylase activity, suppresses cellular levels of polyamines and inhibits cell growth. Biochem. J. 304:183; 1993.
10. Sakata, K.; Kashiwagi, K.; Igarashi, K. Properties of a polyamine transporter regulated by antizyme. Biochem. J. 347:297; 2000.
11. Ivanov, I. P.; Matsufuji, S.; Murakami, Y.; Gesteland, R. F.; Atkins, J. F. Conservation of polyamine regulation by translational frame-shifting from yeast to mammals. EMBO J. 19:1907-1917; 2000.
12. Zhu, C.; Lang, D. W.; Coffino, P. Antizyme 2 is a negative regulator of ornithine decarboxylase and polyamine transport. J. Biol. Chem. 274:26425; 1999.
13. Felschow, D. M.; Mi, Z.; Stanek, J.; Frei, J.; Porter, C. W. Selective labelling of cell-surface polyamine-binding proteins on leukaemic and solid-tumour cell types using a new polyamine photoprobe. Biochem. J. 328:889; 1997.
14. Igarashi, K.; Kashiwagi, K. Polyamines: Mysterious modulators of cellular functions. Biochem. Biophys. Res. Commun. 271:559; 2000.
15. Feuerstein, B. G.; Pattabiraman, N.; Marton, L. J. Molecular dynamics of spermine-DNA interactions: Sequence specificity and DNA bending for a simple ligand. Nucleic Acids Res. 17:6883; 1989.
16. Egli, M.; Williams, L. D.; Gao, Q.; Rich, A. Structure of the pure-spermine form of Z-DNA (magnesium free) at 1-A resolution. Biochemistry 30:11388; 1991.
17. Bloomfield, V. A. DNA condensation by multivalent cations. Biopolymers 44:269; 1997.
18. Raspaud, E.; Chaperon, I.; Leforestier, A.; Livolant, F. Spermine-induced aggregation of DNA, nucleosome, and chromatin. Biophys. J. 77:1547; 1999.
19. Saminathan, M.; Antony, T.; Shirahata, A.; Sigal, L. H.; Thomas, T.; Thomas, T. J. Ionic and structural specificity effects of natural and synthetic polyamines on the aggregation and resolubilization of single-, double-, and triple-stranded DNA. Biochemistry 38:3821; 1999.
20. 2+ in 15-year old crystals. J. Mol. Biol. 301:401; 2000.
21. Usherwood, P. N. Natural and synthetic polyamines: Modulators of signalling proteins. Farmacology 55:202; 2000.
22. Williams, K. Interactions of polyamines with ion channels. Biochem. J. 325:289; 1997.
23. + channels. Eur. J. Biochem. 267:5824; 2000.
24. Lynch, J. W. Rectification of the olfactory cyclic nucleotide-gated channel by intracellular polyamines. J. Membr. Biol. 170:213; 1999.
25. Johnson, T. D. Polyamines and cerebral ischemia. Prog. Drug Res. 50:193; 1998.
26. Zheliaskova, A.; Naydenova, S.; Petrov, A. G. Interaction of phospholipid bilayers with polyamines of different length. Eur. Biophys. J. 29:153; 2000.
27. McCormack, S. A.; Johnson, L. R. Polyamines and cell migration. J. Physiol. Pharmacol. 52:327; 2001.
28. Celano, P.; Baylin, S. B.; Casero, R. A., Jr. Polyamines differentially modulate the transcription of growth-asscoiated genes in human colon carcinoma cells. J. Biol. Chem. 264:8922; 1989.
29. Bachrach, U.; Wang, Y. C.; Tabib, A. Polyamines: New cues in cellular signal transduction. News Physiol. Sci. 16:106; 2001.
30. Patel, A. R.; Wang, J. Y. Polyamines modulate transcription but not posttranscription of c-myc and c-jun in IEC-6 cells. Am. J. Physiol. 273:C1020; 1997.
31. Shah, N.; Thomas, T. J.; Lewis, J. S.; Klinge, C. M.; Shirahata, A.; Gelinas, C.; Thomas, T. Regulation of estrogenic and nuclear factor κB functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells. Oncogene 20:1715; 2001.
32. Hobbs, C. A.; Paul, B. A.; Gilmour, S. K. Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors. Cancer Res. 62:67; 2002.
33. Wang, Y.; Devereux, W.; Woster, P. M.; Casero, R. A., Jr. Cloning and characterization of the mouse polyamine-modulated factor-1 (mPMF-1) gene: An alternatively spliced homologue of the human transcription factor. Biochem. J. 359:387; 2001.
34. Thomas, T.; Kulkarni, G. D.; Gallo, M. A.; Greenfield, N.; Lewis, J. S.; Shirahata, A.; Thomas, T. J. Effects of natural and synthetic polyamines on the conformation of an oligodeoxyribonucleotide with the estrogen response element. Nucleic Acids Res. 25:2396; 1997.
35. Shah, N.; Thomas, T.; Shirahata, A.; Sigal, L. H.; Thomas, T. J. Activation of nuclear factor κB by polyamines in breast cancer cells. Biochemistry 38:14763; 1999.
36. Khan, A. U.; Di Mascio, P.; Medeiros, M. H.; Wilson, T. Spermine and spermidine protection of plasmid DNA against single-strand breaks induced by singlet oxygen. Proc. Natl. Acad. Sci. USA 89:11428; 1992.
37. Khan, A. U.; Mei, Y. H.; Wilson, T. A proposed function for spermine and spermidine: Protection of replicating DNA against damage by singlet oxygen. Proc. Natl. Acad. Sci. USA 89:11426; 1992.
38. Brune, B.; Hartzell, P.; Nicotera, P.; Orrenius, S. Spermine prevents endonuclease activation and apoptosis in thymocytes. Exp. Cell Res. 195:323; 1991.
39. Grassilli, E.; Desiderio, M. A.; Bellesia, E.; Salomoni, P.; Benatti, F. ; Francheschi, C. Is polyamine decrease a common feature of apoptosis? Evidence from γ-rays- and heat shock-induced cell death. Biochem. Biophys. Res. Commun. 216:708; 1995.
40. Lee, Y. B.; Joe, Y. A.; Wolff, E. C.; Dimitriadis, E. K.; Park, M. H. Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor. Biochem. J. 340:273; 1999.
41. Tome, M. E.; Fiser S. M.; Payne, C. M.; Gerner, E. W. Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5A(eIF-5A) and induces apoptosis. Biochem. J. 328:847; 1997.
42. Xu, A.; Chen, K. Y. Hypusine is required for a sequence-specific interaction of eukaryotic initiation factor 5A with postsystematic evolution of ligands by exponential enrichment of RNA. J. Biol. Chem. 276:2555; 2001.
43. Sasaki, K.; Abid, M. R.; Miyazaki, M. Deoxyhypusine synthase gene is essential for cell viability in the yeast Saccharomyces cerevisiae. FEBS Lett. 384:51; 1996.
44. Ahmed, K.; Goueli, S. A.; Williams-Ashman, H. G. Mechanisms and significance of polyamine stimulation of various protein kinase reactions. Adv. Enzyme Regul. 25:401; 1986.
45. Cochet, C.; Chambaz, E. M. Polyamine-mediated protein phosphorylations: A possible target for intracellular polyamine action. Mol. Cell. Endocrinol. 30:247; 1983.
46. Leryo, D.; Heriche, J. K.; Filhol, O.; Chambaz, E. M.; Cochet, C. Binding of polyamines to an autonomous domain of the regulatory subunit of protein kinase CK2 induces a conformational change in the holoenzyme. A proposed role for the kinase stimulation. J. Biol. Chem. 272:20820; 1997.
47. Manni, A.; Wechter, R.; Verderame, M. F.; Mauger, D. Cooperativity between the polyamine pathway and HER-2/neu in transformation of human mammary epithelial cells in culture: Role of the MAPK pathway. Int. J. Cancer 76:563; 1998.
48. Scalabrino, G.; Ferioli, M. E. Degree of enhancement of polyamine biosynthetic decarboxylase activities in human tumors: A useful new index of degree of malignancy. Cancer Detect. Prevent. 8:11; 1985.
49. Canizares, F.; Salinas, J.; De Las Heras, M.; Diaz, J.; Tovar, I.; Martinez, P.; Penafiel, R. Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: Correlation with clinicopathologic parameters. Clin. Cancer Res. 5:2035; 1999.
50. Mohan, R. R.; Challa, A.; Gupta, S.; Bostwick, D. G.; Ahmad, N.; Agarwal, R.; Marengo, S. R.; Amini, S. B.; Paras, F.; MacLennan, G. T.; Resnick, M. I.; Mukhtar, H. Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans. Clin. Cancer Res. 5:143; 1999.
51. Leveque, J.; Bansard, J. Y.; Watier, E.; Catros-Quemener, V.; Havouis, R.; Moulinoux, J. P.; Grall, J. Y.; Seiler, N. Polyamines in human breast cancer and its relations to classical prognostic features: Clinical implications. Anticancer Res. 19:2275; 1999.
52. Leveque, J.; Foucher, F.; Bansard, J. Y.; Havouis, R.; Grall, J. Y.; Moulinoux, J. P. Polyamine profiles in tumor, normal tissue of the homologous breast, blood, and urine of breast cancer sufferers. Breast Cancer Res. Treat. 60:99; 2000.
53. Leveque, J.; Foucher, F.; Havouis, R.; Desury, D.; Grall, J. Y.; Moulinoux, J. P. Benefits of complete polyamine deprivation in hormone responsive and hormone resistant MCF-7 human breast adenocarcinoma in vivo. Anticancer Res. 20:97; 2000.
54. Moshier, J. A.; Dosescu, J.; Skunca, M.; Luk, G. D. Transformation of NIH/3T3 cells by ornithine decarboxylase overexpression. Cancer Res. 53:2618; 1993.
55. Auvinen, M.; Laine, A.; Paasinen-Sohns, A.; Kangas, A.; Kangas, L.; Saksela, O.; Andersson, L. C.; Holtta, E. Human ornithine decarboxylase-overproducing NIH3T3 cells induce rapidly growing, highly vascularized tumors in nude mice. Cancer Res. 57:3016; 1997.
56. McCann, P. P.; Pegg, A. E.; Sjoerdsma, A. (eds.) Inhibition of polyamine metabolism. Biological significance and basis for new therapies. New York: Academic Press; 1987.
57. Williams-Ashman, H. G.; Schenone, A. Methyl glyoxal (bisguanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylase. Biochem. Biophys. Res. Commun. 46:288; 1972.
58. Regenass, U.; Mett, H.; Stanek, J.; Mueller, M.; Kramer, D.; Porter, C. W. CGP 48664, a new S-adenosylmethionine decarboxylase inhibitor with broad spectrum antiproliferative and antitumor activity. Cancer Res. 54:3210; 1994.
59. Thomas, T.; Faaland, C. A.; Adhikarakunnathu, S.; Thomas, T. J. Structure-activity relations of S-adenosylmethionine decarboxylase inhibitors on the growth of MCF-7 breast cancer cells. Breast Cancer Res. Treat. 39:293; 1996.
60. Davis, R. H.; Morris, D. R.; Coffino, P. Sequestered end products and enzyme regulation: The case of ornithine decarboxylase. Microbiol. Rev. 56:280; 1992.
61. Pera, P. J.; Kramer, D. L.; Sufrin, J. R.; Porter, C. W. Comparison of the biological effects of four irreversible inhibitors of ornithine decarboxylase in two murine lymphocytic leukemia cell lines. Cancer Res. 46:1148; 1986.
62. Watanabe, S.; Kusama-Eguchi, K.; Kobayashi, H.; Igarashi, K. Estimation of polyamine binding to macromolecules and ATP in bovine lymphocytes and rat liver. J. Biol. Chem. 266:20803; 1991.
63. Delzenne, N. M.; Kok, N.; Deloyer, P.; Dandrifosse, G. Dietary fructans modulate polyamine concentration in the cecum of rats. J. Nutr. 130:2456; 2000.
64. Seiler, N.; Delcros, J. G.; Moulinox, J. P. Polyamine transport in mammalian cells. An update. Int. J. Biochem. Cell Biol. 28:843; 1996.
65. Byers, T. L.; Pegg, A. E. Regulation of polyamine transport in Chinese hamster ovary cells. J. Cell. Physiol. 143:460; 1990.
66. Igarashi, K.; Kashiwagi, K. Polyamine transport in bacteria and yeast. Biochem. J. 344:633; 1999.
67. Erez, O.; Kahana, C. Screening for modulators of spermine tolerance identifies Skyl, the SR protein kinase of Saccharomyces cerevisiae, as a regulator of polyamine transport and ion homeostasis. Mol. Cell. Biol. 21:175; 2001.
68. Dot, J.; Lluch, M.; Blanco, I.; Rodriguez-Alvarez, J. Polyamine uptake in cultured astrocytes: Characterization and modulation by protein kinases. J. Neurochem. 75:1917; 2000.
69. Kaouass, M.; Audette, M.; Ramotar, D.; Torossian, K.; Gamache, I.; Demontigny, D.; Verma, S.; Poulin, R. The STK2 gene, which encodes a putative Ser/Thr protein kinase, is required for high-affinity spermidine transport in Saccharomyces cerevisiae. Mol. Cell. Biol. 17:2994; 1997.
70. Nozaki, T.; Nishimura, K.; Michael, A. J.; Maruyama, T.; Kakinuma, Y.; Igarashi, K. A second gene encoding a putative serine/threonine protein kinase which enhances spermine uptake in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 228:452; 1996.
71. Poulin, R.; Lessard, M.; Zhao, C. Inorganic cation dependence of putrescine and spermidine transport in human breast cancer cells. J. Biol. Chem. 270:1695; 1995.
72. Erdman, S. H.; Ignatenko, N. A.; Powell, M. B.; Blohm-Mangone, K. A.; Holubec, H.; Guillen-Rodriguez, J. M.; Gerner, E. W. APC-dependent changes in expression of genes influencing polyamine metabolism, and consequences for gastrointestinal carcinogenesis, in the Min mouse. Carcinogenesis 20:1709; 1999.
73. Kramer, D. L.; Miller, J. T.; Bergeron, R. J.; Khomutov, R.; Khomutov, A.; Porter, C. W. Regulation of polyamine transport by polyamines and polyamine analogs. J. Cell. Physiol. 155:399; 1993.
74. Faaland, C. A.; Thomas, T. J.; Balabhadrapathruni, S.; Langer, T.; Mian, S.; Shirahata, A.; Gallo, M. A.; Thomas, T. Molecular correlates of the action of bis(ethyl)polyamines in breast cancer cell growth inhibition and apoptosis. Biochem. Cell Biol. 78:415-426; 2000.
75. 11-diethylnorspermine. Drug Metab. Dispos. 23:1117; 1995.
76. Muller, S.; Luchow, A.; McCann, P. P.; Walter, R. D. Effect of bis(benzyl)polyamine derivatives on polyamine transport and survival of Brugia pahangi. Parasitol. Res. 77:612; 1991.
77. Metcalf, B. W.; Bey, P.; Danzin, C.; Jung, M. J.; Casara, P. Catalytic irreversible inhibition of mammalian ornithine decarboxylase. J. Am. Chem. Soc. 100:2551; 1978.
78. Abeloff, M. D.; Rosen, S. T.; Luk, G. D.; Baylin, S. B.; Zeltzman, M.; Sjoerdsma, A. Phase II trials of α-difluoromethylornithine, an inhibitor of polyamine synthesis in advanced small lung cancer and colon cancer. Cancer Treat. Rep. 70:843; 1986.
79. Meyskens, F. L., Jr.; Gerner, E. W.; Emerson, S.; Pelot, D.; Durbin, T.; Doyle, K.; Lagerberg, W. Effect of α-difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double-blinded trial for colon cancer prevention. J. Natl. Cancer Inst. 90:1212; 1998.
80. Meyskens, F. L., Jr.; Gerner, E. W. Development of difluoromethylornithine (DFMO) as a chemoprevention agent. Clin. Cancer Res. 5:945; 1999.
81. Casero, R. A., Jr.; Woster, P. M. Terminally alkylated polyamine analogues as chemotherapeutic agents. J. Med. Chem. 44:1; 2001.
82. Israel, M.; Zoll, E. C.; Muhammad, N.; Modest, E. J. Synthesis and antitumor evaluation of the presumed cytotoxic metabolites of spermine and N,N′-bis(3-aminopropyl)nonane-1,9-diamine. J. Med. Chem. 16:1; 1973.
83. Porter, C. W.; Bergeron, R. J. Spermidine requirement for cell proliferation in eukaryotic cells: Structural specificity and quantitation. Science 219:1083; 1983.
84. Singh, A. B.; Thomas, T. J.; Thomas, T.; Singh, M.; Mann, R. A. Differential effects of polyamine homologues on the prevention of DL-α-difluoromethylornithine-mediated inhibition of malignant cell growth and normal immune response. Cancer Res. 52:1840; 1992.
85. Thomas, T.; Thomas, T. J. Estradiol control of ornithine decarboxylase mRNA, enzyme activity, and polyamine levels in MCF-7 breast cancer cells: Therapeutic implications. Breast Cancer Res. Treat. 29:189; 1994.
86. Porter, C. W.; McManis, J.; Casero, R. A.; Bergeron, R. J. Relative abilities of bis(ethyl) derivatives of putrescine, spermidine, and spermine to regulate polyamine biosynthesis and inhibit L1210 leukemia cell growth. Cancer Res. 47:2821; 1987.
87. Porter, C. W.; Bergeron, R. J. Enzyme regulation as an approach to interference with polyamine biosynthesis - an alternative to enzyme inhibition. Adv. Enzyme Regul. 27:57; 1988.
88. 1-acetyltransferase activity by novel spermine analogs. Mol. Pharmacol. 52:69; 1997.
89. 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. 56:5624; 1996.
90. Reddy, V. K.; Sarkar, A.; Valasinas, A.; Marton, L. J.; Basu, H. S.; Frydman, B. cis-Unsaturated analogues of 3,8,13,18,23-pentaazapentacosane (BE-4-4-4-4): Synthesis and growth inhibitory effects on human prostate cancer cell lines. J. Med. Chem. 44:404; 2001.
91. Hu, R. H.; Pegg, A. E. Rapid induction of apoptosis by deregulated uptake of polyamine analogues. Biochem. J. 328:307; 1997.
92. 11-bis(ethyl)norspermine. Clin. Cancer Res. 5:1638; 1999.
93. 11-diethylnorspermine in patients with non-small cell lung cancer. Clin. Cancer Res. 8:684; 2002.
94. 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. 2:441; 1996.
95. 12-bis(ethyl)spermine in small cell lung cancer cells is maintained in cells expressing the c-myc and Ha-ras oncogenes. Clin. Cancer Res. 4:1557; 1998.
96. 1-acetyltransferase in human lung cancer cells by the bis(ethyl)polyamine analogues. Cancer Res. 49:3829; 1989.
97. 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. USA 94:11557; 1997.
98. 1-acetyltransferase without cytotoxicity by the growth-supporting polyamine analogue 1,12-dimethylspermine. J. Cell Physiol. 165:71; 1995.
99. 11-diethylnorspermine administered by multiple injection or continuous infusion. Clin. Cancer Res. 1:847; 1995.
100. Levin, V. A.; Prados, M. D.; Yung, W. K.; Gleason, M. J.; Ictech, S.; Malec, M. Treatment of recurrent gliomas with eflornithine. J. Natl. Cancer Inst. 84:1432; 1992.
101. Basu, H. S.; Marton, L. J.; Pellarin, M.; Deen, D. F.; McManis, J. S.; Liu, C. Z.; Bergeron, R. J.; Feuerstein, B. G. Design and testing of novel cytotoxic polyamine analogues. Cancer Res. 54:6210; 1994.
102. 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. 36:411; 1995.
103. Basu, H. S.; Pellarin, M.; Feuerstein, B. G.; Shirahata, A.; Samejima, K.; Deen, D. F.; Marton, L. J. Interaction of a polyamine analogue, 1,19-bis-(ethylamino)-5,10,15- triazanonadecane (BE-4-4-4-4), with DNA and effect on growth, survival, and polyamine levels in seven human brain tumor cell lines. Cancer Res. 53:3948; 1993.
104. 14-bis-(ethyl)-homospermine (BE-4-4-4) on the growth of U-251 MG and SF-188 human brain tumor cells. Int. J. Cancer 48:873; 1991.
105. Basu, H. S.; Pellarin, M.; Feuerstein, B. G.; Marton, L. J. The ability of polyamine analogues to induce Z-DNA structure in synthetic polynucleotides in vitro inversely correlates with their effects on cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in human brain tumor cell lines. Anticancer Res. 16:39; 1996.
106. 14-bis(ethyl)homospermine. Int. J. Radiat. Oncol. Biol. Phys. 29:1041; 1994.
107. Smirnov, I. V.; Feuerstein, B. G.; Pellarin, M.; Marton, L. J.; Deen, D. F.; Basu, H. S. Pretreatment with the polyamine analog 1,19-bis-(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) inhibits etoposide cytotoxicity in U-251 MG (NCI) human brain tumor cells. Cell Mol. Biol. 40:975; 1994.
108. Alhonen-Hongisto, L.; Hung, D. T.; Deen, D. F.; Marton, L. J. Decreased cell kill of vincristine and methotrexate against 9L rat brain tumor cells in vitro caused by α-difluoromethylornithine-induced polyamine depletion. Cancer Res. 44:4440; 1984.
109. Levin, V. A.; Uhm, J. H.; Jaeclke, K. A.; Choucair, A.; Flynn, P. J.; Yung, W. K. A.; Prados, M. D.; Bruner, J. M.; Chang, S. M.; Kyritsis, A. P.; Gleason, M. J.; Hess, K. R. Phase III randomized study of postradiotherapy chemotherapy with α -difluoromethylornithine-procarbazine,N-(2-chloroethyl)-N′ -cyclohexyl-N-nitrosurea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme. Clin. Cancer Res. 6:3878; 2000.
110. 3H] spermidine by 9L rat brain tumors after direct intratumoral infusion of inhibitors of enzymes of the polyamine biosynthetic pathway. J. Neurooncol. 42:123; 1999.
111. Chen, Y.; Kramer, D. L.; Diegelman, P.; Vujcic, S.; Porter, C. W. Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells. Cancer Res. 61:6437; 2001.
112. 1-acetyltransferase in MALME-3M human melanoma cells. J. Biol. Chem. 268:19118; 1993.
113. Bernacki, R. J.; Bergeron, R. J.; Porter, C. W. Antitumor activity of N,N′-bis(ethyl)spermine homologues against human MALME-3 melanoma xenografts. Cancer Res. 52:2424; 1992.
114. 1-acetyltransferase gene expression. Biochemistry 35:14436; 1996.
115. Wang, Y.; Devereux, W.; Stewart, T. M.; Casero, R. A., Jr. Cloning and characterization of human polyamine-modulated factor-1, a transcriptional cofactor that regulates the transcription of the spermidine/spermine N(1)-acetyltransferase gene. J. Biol. Chem. 274:22095; 1999.
116. 11-diethylnorspermine. Cancer Res. 54:5917; 1994.
117. Kramer, D. L.; Vujcic, S.; Diegelman, P.; Alderfer, J.; Miller, J. T.; Black, J. D.; Bergeron, R. J.; Porter, C. W. Polyamine analogue induction of the p53-p21WAF1/CIP1-Rb pathway and G1 arrest in human melanoma cells. Cancer Res. 59:1278; 1999.
118. Henderson, B. E.; Ross, R. Estrogens as a cause of human cancer. Cancer Res. 48:246-253; 1988.
119. Glikman, P.; Manni, A.; Demers, L.; Bartholomew, M. Polyamine involvement in the growth of hormone-responsive and -resistant human breast cancer cells in culture. Cancer Res. 49:1371; 1989.
120. Manni, A. The role of polyamines in the hormonal control of breast cancer cell proliferation. Cancer Treat. Res. 71:209; 1994.
121. Manni, A.; Grove, R.; Kunselman, S.; Aldaz, M. Involvement of the polyamine pathway in breast cancer progression. Cancer Lett. 92:49; 1995.
122. 5dC) and a plasmid containing the estrogen response element. J. Steroid Biochem. Mol. Biol. 54:89; 1995.
123. 12-bis(ethyl)spermine. Cancer Res. 53:2071; 1993.
124. 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. Related Cancer 6:69; 1999.
125. Hahm, H. A.; Dunn, V. R.; Butash, K. A.; Deveraux, W. L.; Woster, P. M.; Casero, R. A., Jr.; Davidson, N. E. Combination of standard cytotoxic agents with polyamine analogues in the treatment of breast cancer cell lines. Clin. Cancer Res. 7:391; 2001.
126. Shah, N.; Antony, T.; Haddad, S.; Amenta, P.; Shirahata, A.; Thomas, T. J.; Thomas, T. Antitumor effects of bis(ethyl)polyamine analogs on mammary tumor development in FVB/NTgN (MMTVneu) transgenic mice. Cancer Lett. 146:15; 1999.
127. 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. 40:172; 1997.
128. Mi, Z.; Kramer, D. L.; Miller, J. T.; Bergeron, R. J.; Bernacki, R.; Porter, C. W. Human prostatic carcinoma cell lines display altered regulation of polyamine transport in response to polyamine analogs and inhibitors. Prostate 34:51; 1998.
129. Zagaja, G. P.; Shrivastav, M.; Fleig, M. J.; Marton, L. J.; Rinker-Schaeffer, C. W.; Dolan, M. E. Effects of polyamine analogues on prostatic adenocarcinoma cells in vitro and in vivo. Cancer Chemother. Pharmacol. 41:505; 1998.
130. 11-diethylnorspermine against human prostate carcinoma cells. Prostate 44:313; 2000.
131. 1-ethylN-11-((cycloheptyl)methyl)-4,8-diazaundecane in human prostate cancer cells. Clin. Cancer Res. 6:17; 2000.
132. 14N-bisethylhomospermine (BE-4-4-4): Synthesis and growth inhibitory effects on human prostate cancer cells. J. Med. Chem. 44:390; 2001.
133. Heston, W. D.; Yang, C. R.; Pliner, L.; Russo, P.; Covey, D. F. Cytotoxic activity of a polyamine analogue, monoaziridinylputrescine, against the PC-3 human prostatic carcinoma cell line. Cancer Res. 47:3627; 1987.
134. Eiseman, J. L.; Rogers, F. A.; Guo, Y.; Kauffman, J.; Sentz, D. L.; Klinger, M. F.; Callery, P. S.; Kyprianou, N. Tumor-targeted apoptosis by a novel spermine analogue, 1,12-diaziridinyl-4,9-diazadodecane, results in therapeutic efficacy and enhanced radiosensitivity of human prostate cancer. Cancer Res. 58:4864; 1998.
135. Dolan, M. E.; Fleig, M. J.; Feuerstein, B. G.; Basu, H. S.; Luk, G. D.; Casero, R. A., Jr.; Marton, L. J. Effect of 1,19-bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts. Cancer Res. 54:4698; 1994.
136. Chang, B. K.; Bergeron, R. J.; Porter, C. W.; Vinson, J. R.; Liang, Y.; Libby, P. R. Regulatory and antiproliferative effects of N-alkylated polyamine analogues in human and hamster pancreatic adenocarcinoma cell lines. Cancer Chemother. Pharmacol. 30:183; 1992.
137. Chang, B. K.; Bergeron, R. J.; Porter, C. W.; Liang, Y. Antitumor effects of N-alkylated polyamine analogues in human pancreatic adenocarcinoma models. Cancer Chemother. Pharmacol. 30:179; 1992.
138. Chang, B. K.; Liang, Y.; Miller, D. W.; Bergeron, R. J.; Porter, C. W.; Wang, G. Effects of diethyl spermine analogues in human bladder cancer cell lines in culture. J. Urol. 150:1293; 1993.
139. Sharma, A.; Glaves, D.; Porter, C. W.; Raghavan, D.; Bernacki, R. J. Antitumor efficacy of N1,N11-diethylnorspermine on a human bladder tumor xenograft in nude athymic mice. Clin. Cancer Res. 3:1239; 1997.
140. 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. 44:2451; 2001.
141. 1-acetylspermine. Biochim. Biophys. Acta 1381:89; 1998.
142. 12-bis(ethyl)spermine is preceded by a reduction in MYC oncoprotein levels. J. Cell Physiol. 174:380; 1998.
143. 11-bis(ethyl)norspermine against human melanoma xenografts and possible biochemical correlates of drug action. Cancer Res. 53:581; 1993.
144. 11-diethylnorspermine) in rats and dogs. Anticancer Drugs 5:448; 1994.
145. 11-diethylnorspermine in patients with advanced malignancy. Invest. New Drugs 15:227; 1997.
146. 11-diethylnorspermine in a Cebus apella primate model. Cancer Res. 60:4433; 2000.
147. 14-diethylhomospermine. Drug Metab. Dispos. 24:334; 1996.
148. Thomas, T. J.; Messner, R. P. Structural specificity of polyamines in left-handed Z-DNA formation. Immunological and spectroscopic studies. J. Mol. Biol. 201:463; 1988.
149. Basu, H. S.; Smirnov, I. V.; Peng, H. F.; Tiffany, K.; Jackson, V. Effects of spermine and its cytotoxic analogs on nucleosome formation on topologically stressed DNA in vitro. Eur. J. Biochem. 243:247; 1997.
150. Thomas, T. J.; Bloomfield, V. A. Collapse of DNA caused by trivalent cations: pH and ionic specificity effects. Biopolymers 22:1097; 1983.
151. Vijayanathan, V.; Thomas, T.; Shirahata, A.; Thomas, T. J. DNA condensation by polyamines: A laser light scattering study of structural effects. Biochemistry 40:13644; 2001.
152. Saminathan, M.; Thomas, T.; Shirahata, A.; Pillai, C. K. S.; Thomas, T. J. Polyamine structural effects on the induction and stabilization of liquid crystalline DNA: Potential applications to DNA packaging, gene therapy and polyamine therapeutics. Nucleic Acids Res. 30:3722; 2002.
153. Panagiotidis, C. A.; Artandi, S.; Calame, K.; Silverstein, S. J. Polyamines alter sequence-specific DNA-protein interactions. Nucleic Acids Res. 23:1800; 1995.
154. Maeda, Y.; Rachez, C.; Hawel, L., 3rd., Byus, C. V.; Freedman, L. P.; Sladek, F. M. Polyamines modulate the interaction between nuclear receptors and vitamin d receptor-interacting protein 205. Mol. Endocrinol. 16:1502; 2002.
155. Webb, H. K.; Wu, Z.; Sirisoma, N.; Ha, H. C.; Casero, R. A., Jr.; Woster,
156. Dai, H.; Kramer, D. L.; Yang, C.; Murti, K. G.; Porter, C. W.; Cleveland, J. L. The polyamine oxidase inhibitor MDL-72,527 selectively induces apoptosis of transformed hematopoietic cells through lysosomotropic effects. Cancer Res. 59:4944; 1999.
157. Stancovski, I.; Baltimore, D. NF-κB activation: The IκB kinase revealed? Cell 91:299; 1997.
158. 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. USA 95:11140; 1998.
159. 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. 58:2711; 1998.
160. He, Y.; Suzuki, T.; Kashiwagi, K.; Kusama-Eguchi, K.; Shirahata, A.; Igarashi, K. Correlation between the inhibition of cell growth by bis(ethyl)polyamine analogues and the decrease in the function of mitochondria. Eur. J. Biochem. 221:391; 1994.
161. 12-bis(ethyl)spermine. Biochem. J. 291:131; 1993.
162. 12-bis(ethyl)spermine effect on growth of cis-diamminedichloroplatinum(II)-sensitive and -resistant human ovarian-carcinoma cell lines. Int. J. Cancer 78:33; 1998.
163. Kakinuma, Y.; Hoshino, K.; Igarashi, K. Characterization of the inducible polyamine transporter in bovine lymphocytes. Eur. J. Biochem. 176: 409; 1988.
164. Hyvonen, T.; Seiler, N.; Persson, L. Characterization of a COS cell line deficient in polyamine transport. Biochim. Biophys. Acta 1221:279; 1994.
165. Minchin, R. F.; Martin, R. L.; Summers, L. A.; Ilett, K. F. Inhibition of putrescine uptake by polypyridinium quaternary salts in B16 melanoma cells treated with difluoromethylornithine. Biochem. J. 262:391; 1989.
166. Porter, C. W.; Miller, J.; Bergeron, R. J. Aliphatic chain length specificity of the polyamine transport system in ascites L1210 leukemia cells. Cancer Res. 44:126; 1984.
167. Nicolet, T.; Scemama, J. L.; Pradayro, L.; Berthelemy, P.; Seva, C.; Vaysse, N. Putrescine and spermidine uptake is regulated by proliferation and dexamethasone treatment in AR4-2J cells. Int. J. Cancer 49:577; 1991.
168. Lessard, M.; Zhao, C.; Singh, S. M.; Poulin, R. Hormonal and feedback regulation of putrescine and spermidine transport in human breast cancer cells. J. Biol. Chem. 270:1685; 1995.
169. Gundogus-Ozcanli, N.; Sayilir, C.; Criss, W. E. Effects of polyamines, polyamine synthesis inhibitors, and polyamine analogs on casein kinase II using Myc oncoprotein as substrate. Biochem. Pharmacol. 58:251; 1999.