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[Cancer Research 48, 759-774, February 15, 1988]
© 1988 American Association for Cancer Research

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Polyamine Metabolism and Its Importance in Neoplastic Growth and as a Target for Chemotherapy1

Anthony E. Pegg

Departments of Physiology and Pharmacology and Cancer Research Center, Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

The polyamine-biosynthetic pathway represents an inviting target for the development of agents inhibiting carcinogenesis and tumor growth. Polyamines play an essential role in the proliferation and development of mammalian cells. Deranged polyamine metabolism may be an important factor in carcinogenesis. Depletion of polyamines inhibits growth of neoplastic cells in vitro and in animal models. Several different classes of other anticancer agents may under some conditions exert enhanced effects when polyamine levels are depleted. Some suitable inhibitors of polyamine production are currently available and other promising compounds are presently being tested. It should soon prove possible to block polyamine biosynthesis at every step in the pathway. The use of these inhibitors alone and combined either with each other or with other antitumor agents will enable a full examination of the potential of this approach.

1 Research on polyamines in the author's laboratory was supported by Grants CA-18138, GM-26290, and CA-37606 from the NIH.

Received 10/14/87. Accepted 11/10/87.




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Clin. Cancer Res.Home page
H. A. Hahm, D. S. Ettinger, K. Bowling, B. Hoker, T. L. Chen, Y. Zabelina, and R. A. Casero Jr.
Phase I Study of N1,N11-Diethylnorspermine in Patients with Non-Small Cell Lung Cancer
Clin. Cancer Res., March 1, 2002; 8(3): 684 - 690.
[Abstract] [Full Text] [PDF]


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BloodHome page
T. Nemoto, H. Hori, M. Yoshimoto, Y. Seyama, and S. Kubota
Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression
Blood, February 15, 2002; 99(4): 1478 - 1481.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
M.-H. Hou, S.-B. Lin, J.-M. P. Yuann, W.-C. Lin, A. H.-J. Wang, and L.-s. Kan
Effects of polyamines on the thermal stability and formation kinetics of DNA duplexes with abnormal structure
Nucleic Acids Res., December 15, 2001; 29(24): 5121 - 5128.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
P. M. Bauer, G. M. Buga, and L. J. Ignarro
Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide
PNAS, October 5, 2001; (2001) 211443198.
[Abstract] [Full Text] [PDF]


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Am. J. Pathol.Home page
N. Ahmad, A. C. Gilliam, S. K. Katiyar, T. G. O'Brien, and H. Mukhtar
A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis
Am. J. Pathol., September 1, 2001; 159(3): 885 - 892.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
V. Robert, B. Mouille, C. Mayeur, M. Michaud, and F. Blachier
Effects of the garlic compound diallyl disulfide on the metabolism, adherence and cell cycle of HT-29 colon carcinoma cells: evidence of sensitive and resistant sub-populations
Carcinogenesis, August 1, 2001; 22(8): 1155 - 1161.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
B. H. Chung, S. H. Mitchell, J.-S. Zhang, and C. Y. F. Young
Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells
Carcinogenesis, August 1, 2001; 22(8): 1201 - 1206.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
D. J. Feith, L. M. Shantz, and A. E. Pegg
Targeted Antizyme Expression in the Skin of Transgenic Mice Reduces Tumor Promoter Induction of Ornithine Decarboxylase and Decreases Sensitivity to Chemical Carcinogenesis
Cancer Res., August 1, 2001; 61(16): 6073 - 6081.
[Abstract] [Full Text] [PDF]


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Biol. Reprod.Home page
C. Rodriguez-Sallaberry, F. A. Simmen, and R. C.M. Simmen
Polyamine- and Insulin-Like Growth Factor-I-Mediated Proliferation of Porcine Uterine Endometrial Cells: A Potential Role for Spermidine/Spermine N1-Acetyltransferase During Peri-Implantation
Biol Reprod, August 1, 2001; 65(2): 587 - 594.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
C.-O. Evans, A. N. Young, M. R. Brown, D. J. Brat, John. S. Parks, A. S. Neish, and N. M. Oyesiku
Novel Patterns of Gene Expression in Pituitary Adenomas Identified by Complementary Deoxyribonucleic Acid Microarrays and Quantitative Reverse Transcription-Polymerase Chain Reaction
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3097 - 3107.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
S. Carnesecchi, Y. Schneider, J. Ceraline, B. Duranton, F. Gosse, N. Seiler, and F. Raul
Geraniol, a Component of Plant Essential Oils, Inhibits Growth and Polyamine Biosynthesis in Human Colon Cancer Cells
J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 197 - 200.
[Abstract] [Full Text]


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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
R. M. Ray, S. A. McCormack, and L. R. Johnson
Polyamine depletion arrests growth of IEC-6 and Caco-2 cells by different mechanisms
Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G37 - G43.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
J. Satriano, M. Isome, R. A. Casero Jr., S. C. Thomson, and R. C. Blantz
Polyamine transport system mediates agmatine transport in mammalian cells
Am J Physiol Cell Physiol, July 1, 2001; 281(1): C329 - C334.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
J. N. Rao, L. Li, V. A. Golovina, O. Platoshyn, E. D. Strauch, J. X.-J. Yuan, and J.-Y. Wang
Ca2+-RhoA signaling pathway required for polyamine-dependent intestinal epithelial cell migration
Am J Physiol Cell Physiol, April 1, 2001; 280(4): C993 - C1007.
[Abstract] [Full Text] [PDF]


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Cancer Epidemiol. Biomarkers Prev.Home page
L. Y. Y. Fong, V. T. Nguyen, A. E. Pegg, and P. N. Magee
{{alpha}}-Difluoromethylornithine Induction of Apoptosis: A Mechanism Which Reverses Pre-established Cell Proliferation and Cancer Initiation in Esophageal Carcinogenesis in Zinc-deficient Rats
Cancer Epidemiol. Biomarkers Prev., March 1, 2001; 10(3): 191 - 199.
[Abstract] [Full Text]


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CirculationHome page
W. Durante, L. Liao, S. V. Reyna, K. J. Peyton, and A. I. Schafer
Transforming Growth Factor-{beta}1 Stimulates L-Arginine Transport and Metabolism in Vascular Smooth Muscle Cells : Role in Polyamine and Collagen Synthesis
Circulation, February 27, 2001; 103(8): 1121 - 1127.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
H. A. Hahm, V. R. Dunn, K. A. Butash, W. L. Deveraux, P. M. Woster, R. A. Casero Jr., and N. E. Davidson
Combination of Standard Cytotoxic Agents with Polyamine Analogues in the Treatment of Breast Cancer Cell Lines
Clin. Cancer Res., February 1, 2001; 7(2): 391 - 399.
[Abstract] [Full Text]


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Mol. Cell. Biol.Home page
O. Erez and C. Kahana
Screening for Modulators of Spermine Tolerance Identifies Sky1, the SR Protein Kinase of Saccharomyces cerevisiae, as a Regulator of Polyamine Transport and Ion Homeostasis
Mol. Cell. Biol., January 1, 2001; 21(1): 175 - 184.
[Abstract] [Full Text]


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Cancer Epidemiol. Biomarkers Prev.Home page
D. S. Alberts, R. T. Dorr, J. G. Einspahr, M. Aickin, K. Saboda, M. J. Xu, Y.-M. Peng, R. Goldman, J. A. Foote, J. A. Warneke, et al.
Chemoprevention of Human Actinic Keratoses by Topical 2-(Difluoromethyl)-dl-ornithine
Cancer Epidemiol. Biomarkers Prev., December 1, 2000; 9(12): 1281 - 1286.
[Abstract] [Full Text]


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J. Bacteriol.Home page
Y. Takatsuka, Y. Yamaguchi, M. Ono, and Y. Kamio
Gene Cloning and Molecular Characterization of Lysine Decarboxylase from Selenomonas ruminantium Delineate Its Evolutionary Relationship to Ornithine Decarboxylases from Eukaryotes
J. Bacteriol., December 1, 2000; 182(23): 6732 - 6741.
[Abstract] [Full Text]


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CarcinogenesisHome page
J. Moffatt, M. Hashimoto, A. Kojima, D. O. Kennedy, A. Murakami, K. Koshimizu, H. Ohigashi, and I. Matsui-Yuasa
Apoptosis induced by 1'-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation
Carcinogenesis, December 1, 2000; 21(12): 2151 - 2157.
[Abstract] [Full Text] [PDF]


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JCBHome page
A. Paasinen-Sohns, M. Kielosto, E. Kaariainen, T. Eloranta, A. Laine, O. A. Janne, M. J. Birrer, and E. Holtta
C-Jun Activation-Dependent Tumorigenic Transformation Induced Paradoxically by Overexpression or Block of S-Adenosylmethionine Decarboxylase
J. Cell Biol., November 13, 2000; 151(4): 801 - 810.
[Abstract] [Full Text] [PDF]


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J. Bacteriol.Home page
K. Limsuwun and P. G. Jones
Spermidine Acetyltransferase Is Required To Prevent Spermidine Toxicity at Low Temperatures in Escherichia coli
J. Bacteriol., October 1, 2000; 182(19): 5373 - 5380.
[Abstract] [Full Text]


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Cancer Res.Home page
L. Lan, C. Trempus, and S. K. Gilmour
Inhibition of Ornithine Decarboxylase (ODC) Decreases Tumor Vascularization and Reverses Spontaneous Tumors in ODC/Ras Transgenic Mice
Cancer Res., October 1, 2000; 60(20): 5696 - 5703.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
P. P. Carbone, J. A. Douglas, J. Thomas, K. Tutsch, M. Pomplun, M. Hamielec, and D. Pauk
Bioavailability Study of Oral Liquid and Tablet Forms of {{alpha}}-Difluoromethylornithine
Clin. Cancer Res., October 1, 2000; 6(10): 3850 - 3854.
[Abstract] [Full Text]


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Cancer Res.Home page
R. J. Bergeron, R. L. Merriman, S. G. Olson, J. Wiegand, J. Bender, R. R. Streiff, and W. R. Weimar
Metabolism and Pharmacokinetics of N ,N11-Diethylnorspermine in a Cebus apella Primate Model
Cancer Res., August 1, 2000; 60(16): 4433 - 4439.
[Abstract] [Full Text]


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J. Nutr.Home page
W. W. and C. M. Higuchi
Dietary Soy Protein Is Associated with Reduced Intestinal Mucosal Polyamine Concentration in Male Wistar Rats
J. Nutr., July 1, 2000; 130(7): 1815 - 1820.
[Abstract] [Full Text]


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Cancer Res.Home page
R. Singh, S. Pervin, A. Karimi, S. Cederbaum, and G. Chaudhuri
Arginase Activity in Human Breast Cancer Cell Lines: N{{omega}}-Hydroxy-L-arginine Selectively Inhibits Cell Proliferation and Induces Apoptosis in MDA-MB-468 Cells
Cancer Res., June 1, 2000; 60(12): 3305 - 3312.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
F. A. L. M. Eskens, G. A. Greim, C. van Zuylen, I. Wolff, L. J. Denis, A. S. Th. Planting, F. A. Muskiet, J. Wanders, N. C. Barbet, L. Choi, et al.
Phase I and Pharmacological Study of Weekly Administration of the Polyamine Synthesis Inhibitor SAM 486A (CGP 48 664) in Patients with Solid Tumors
Clin. Cancer Res., May 1, 2000; 6(5): 1736 - 1743.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
M. A. Hoyt, M. Broun, and R. H. Davis
Polyamine Regulation of Ornithine Decarboxylase Synthesis in Neurospora crassa
Mol. Cell. Biol., April 15, 2000; 20(8): 2760 - 2773.
[Abstract] [Full Text]


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Cancer Epidemiol. Biomarkers Prev.Home page
B. S. Reddy
Novel Approaches to the Prevention of Colon Cancer by Nutritional Manipulation and Chemoprevention
Cancer Epidemiol. Biomarkers Prev., March 1, 2000; 9(3): 239 - 247.
[Abstract] [Full Text]


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Am. J. Physiol. Cell Physiol.Home page
R. M. Ray, M. J. Viar, Q. Yuan, and L. R. Johnson
Polyamine depletion delays apoptosis of rat intestinal epithelial cells
Am J Physiol Cell Physiol, March 1, 2000; 278(3): C480 - C489.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. H. M. Hoet and B. Nemery
Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions
Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L417 - L433.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. E. Graham, C. L. Bock, C. Schalk-Hihi, Z. J. Lu, and G. D. Markham
Identification of a Highly Diverged Class of S-Adenosylmethionine Synthetases in the Archaea
J. Biol. Chem., February 11, 2000; 275(6): 4055 - 4059.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
E. I. Salim, H. Wanibuchi, K. Morimura, S. Kim, Y. Yano, S. Yamamoto, and S. Fukushima
Inhibitory effects of 1,3-diaminopropane, an ornithine decarboxylase inhibitor, on rat two-stage urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine
Carcinogenesis, February 1, 2000; 21(2): 195 - 203.
[Abstract] [Full Text] [PDF]


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Nephrol Dial TransplantHome page
M. Ketteler, R. Westenfeld, A. Gawlik, E. de Heer, and A. Distler
Acute glomerular upregulation of ornithine decarboxylase is not essential for mesangial cell proliferation and matrix expansion in anti-Thy-1-nephritis
Nephrol. Dial. Transplant., January 1, 2000; 15(1): 16 - 22.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
B. Saverio, D. Pierpaola, A. Serenella, C. Cesare, M. Bruno, T. Auro, and C. Arnaldo
Tumor Progression Is Accompanied by Significant Changes in the Levels of Expression of Polyamine Metabolism Regulatory Genes and Clusterin (Sulfated Glycoprotein 2) in Human Prostate Cancer Specimens
Cancer Res., January 1, 2000; 60(1): 28 - 34.
[Abstract] [Full Text]




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