Ornithine decarboxylase as an enzyme target for therapy.

Interest in ornithine decarboxylase (ODC) and the therapeutic effects of its inhibition with the consequent depletion of polyamine biosynthesis has been widespread since the late 1970s and 1980s. This review covers new information about the properties of ODC, recent findings with ODC inhibitors and a discussion of the mechanism of inactivation of ODC by eflornithine. Recent in vivo therapeutic approaches of ODC inhibition are also discussed including: cancer and cancer chemoprevention; autoimmune diseases; polyamines and the blood-brain barrier, ischemia and hyperplasia; the NMDA receptor and modulation by polyamines; hearing loss; African trypanosomiasis; Pneumocystis carinii pneumonia and Cryptosporidium in AIDS; and other infectious diseases/organisms.

[1]  S. Rogers,et al.  Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. , 1986, Science.

[2]  C. Boone,et al.  Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. , 1990, Cancer research.

[3]  A. Sjoerdsma,et al.  Chemotherapeutic implications of polyamine biosynthesis inhibition , 1984, Clinical pharmacology and therapeutics.

[4]  E. Endean,et al.  Intimal hyperplasia is reduced by ornithine decarboxylase inhibition. , 1991, The Journal of surgical research.

[5]  A. Fairlamb,et al.  Trypanothione is the primary target for arsenical drugs against African trypanosomes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[6]  K. Williams,et al.  Characterization of polyamines having agonist, antagonist, and inverse agonist effects at the polyamine recognition site of the NMDA receptor , 1990, Neuron.

[7]  A. Fairlamb,et al.  In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei. , 1987, Molecular and biochemical parasitology.

[8]  B. Gazzard,et al.  Pneumocystis carinii pneumonia treated with eflornithine in AIDS patients resistant to conventional therapy. , 1990, AIDS.

[9]  B. Metcalf,et al.  Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C.4.1.1.17) by substrate and product analogs , 1978 .

[10]  N. Seiler,et al.  The gastrointestinal tract as polyamine source for tumor growth. , 1989, Anticancer research.

[11]  L. Alhonen,et al.  Human ornithine decarboxylase-encoding loci: nucleotide sequence of the expressed gene and characterization of a pseudogene. , 1990, Gene.

[12]  J. Paris,et al.  Post-transcriptional regulation of ornithine decarboxylase in Xenopus laevis oocytes. , 1990, Development.

[13]  D. Metzler,et al.  A novel reaction of the coenzyme of glutamate decarboxylase with L-serine O-sulfate. , 1982, Biochemistry.

[14]  I. Holm,et al.  Curative effect of DL-2-difluoromethylornithine on mice bearing mutant L1210 leukemia cells deficient in polyamine uptake. , 1988, Cancer research.

[15]  D. Schaid,et al.  Disseminated malignant melanoma and recombinant interferon: analysis of seven consecutive phase II investigations. , 1990, The Journal of investigative dermatology.

[16]  A. Sjoerdsma,et al.  14 – THERAPEUTIC UTILITY OF SELECTED ENZYME-ACTIVATED IRREVERSIBLE INHIBITORS , 1989 .

[17]  L. Ghoda,et al.  Expression and post-transcriptional regulation of ornithine decarboxylase during early Xenopus development. , 1991, European journal of biochemistry.

[18]  A. Verma,et al.  11 – Inhibition of Carcinogenesis by Inhibitors of Putrescine Biosynthesis , 1987 .

[19]  S. Baylin,et al.  6 – Inhibitors of Polyamine Biosynthesis: Cellular and in Vivo Effects on Tumor Proliferation , 1987 .

[20]  A. Pegg,et al.  Identification of residues in ornithine decarboxylase essential for enzymic activity and for rapid protein turnover. , 1991, The Biochemical journal.

[21]  J. Kovacs,et al.  Polyamine metabolism in Pneumocystis carinii. , 1991, The Journal of infectious diseases.

[22]  A. Verma.  The enzyme-activated irreversible inhibitor of ornithine decarboxylase, DL-alpha-difluoromethylornithine: a chemopreventive agent. , 1989, Preventive medicine.

[23]  A. Pegg,et al.  Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. , 1988, Cancer research.

[24]  L. Meeker,et al.  Chemoprevention of mammary carcinogenesis: a comparative review of the efficacy of a polyamine antimetabolite, retinoids, and selenium. , 1986, Journal of the National Cancer Institute.

[25]  P. McCann,et al.  Difluoromethylornithine irreversibly inactivates ornithine decarboxylase of Pseudomonas aeruginosa, but does not inhibit the enzymes of Escherichia coli. , 1981, Biochemical Journal.

[26]  C. Danzin,et al.  1 – Inhibition of Basic Amino Acid Decarboxylases Involved in Polyamine Biosynthesis , 1987 .

[27]  M. Phillips,et al.  Trypanosome ornithine decarboxylase is stable because it lacks sequences found in the carboxyl terminus of the mouse enzyme which target the latter for intracellular degradation. , 1990, The Journal of biological chemistry.

[28]  G. L. Vaaler,et al.  Pyridoxal 5'-phosphate dependent histidine decarboxylase: overproduction, purification, biosynthesis of soluble site-directed mutant proteins, and replacement of conserved residues. , 1989, Biochemistry.

[29]  H. Bernstein,et al.  Ornithine decarboxylase in the inner ear of the guinea pig , 1988, Brain Research Bulletin.

[30]  A. Pegg,et al.  Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites. , 1992, The Journal of biological chemistry.

[31]  Jayashree,et al.  Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. , 1990, Cancer research.

[32]  B. Evers,et al.  Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth. , 1991, Gastroenterology.

[33]  K. Williams,et al.  Polyamines Modulate the Binding of [3H]MK‐801 to the Solubilized N‐Methyl‐D‐Aspartate Receptor , 1991, Journal of neurochemistry.

[34]  W. Brownell,et al.  Cochlear damage and increased threshold in alpha-difluoromethylornithine (DFMO) treated guinea pigs , 1990, Hearing Research.

[35]  G. F. Davis,et al.  Effects of three irreversible inhibitors of ornithine decarboxylase on macrophage-mediated tumoricidal activity and antitumor activity in B16F1 tumor-bearing mice. , 1990, Cancer research.

[36]  J. H. Casseday,et al.  Identification of polyamines in the cochlea of the rat and their potential role in hearing , 1986, Brain Research Bulletin.

[37]  B. Ullman,et al.  Amplification and molecular cloning of the ornithine decarboxylase gene of Leishmania donovani. , 1992, The Journal of biological chemistry.

[38]  G. Kelloff,et al.  Interspecies analysis of the chemopreventive efficacy of dietary alpha-difluoromethylornithine. , 1990, Anticancer research.

[39]  C. Porter,et al.  10 – Modulation of Antineoplastic Drug Action by Inhibitors of Polyamine Biosynthesis , 1987 .

[40]  T. Furuchi,et al.  Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome. , 1991, The Journal of biological chemistry.

[41]  L. Alhonen,et al.  Polyamines: from molecular biology to clinical applications. , 1991, Annals of medicine.

[42]  C. Kahana,et al.  Characterization of sequences involved in mediating degradation of ornithine decarboxylase in cells and in reticulocyte lysate. , 1991, European journal of biochemistry.

[43]  P. Heseltine,et al.  Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. , 1992, Chest.

[44]  P. Mamont,et al.  Anti-proliferative properties of DL-alpha-difluoromethyl ornithine in cultured cells. A consequence of the irreversible inhibition of ornithine decarboxylase. , 1978, Biochemical and biophysical research communications.

[45]  P. McCann,et al.  15 – Parasitic Protozoa and Polyamines , 1987 .

[46]  C. Boone,et al.  Study of postnatal effects of chemopreventive agents on offspring of ethylnitrosourea-induced transplacental carcinogenesis in rats. I. Influence of retinol acetate, alpha-tocopherol acetate, thiamine chloride, sodium selenite, and alpha-difluoromethylornithine. , 1991, Cancer letters.

[47]  P. Coffino,et al.  Mouse ornithine decarboxylase. Complete amino acid sequence deduced from cDNA. , 1985, The Journal of biological chemistry.

[48]  A. Pegg.  12 – INHIBITION OF POLYAMINE BIOSYNTHESIS AND FUNCTION AS AN APPROACH TO DRUG DESIGN , 1989 .

[49]  J. Hamon,et al.  Effects of Mel B Arsobal and alpha-difluoromethylornithine on the awakening electroencephalogram of humans with gambiense trypanosomiasis disease: Preliminary report , 1990, Pharmacology Biochemistry and Behavior.

[50]  S. Baylin,et al.  Ornithine decarboxylase as a biologic marker in familial colonic polyposis. , 1984, The New England journal of medicine.

[51]  P. Mamont,et al.  Comparative antitumor properties in rodents of irreversible inhibitors of L-ornithine decarboxylase, used as such or as prodrugs. , 1989, Cancer research.

[52]  I. Scheffler,et al.  Nucleotide sequence of the Chinese hamster ornithine decarboxylase gene. , 1989, Nucleic acids research.

[53]  R. Campbell,et al.  Effects of DL-alpha-difluoromethylornithine, 4-deoxypyridoxine and methylglyoxal bis(guanylhydrazone) on allograft prolongation. , 1991, Life sciences.

[54]  A. Fairlamb,et al.  Inhibition of polyamine biosynthesis in Crithidia fasciculata by D,L-α-difluoromethylornithine and D,L-α-difluoromethylarginine , 1991 .

[55]  A. Pegg,et al.  Measurement of the number of ornithine decarboxylase molecules in rat and mouse tissues under various physiological conditions by binding of radiolabelled alpha-difluoromethylornithine. , 1982, The Biochemical journal.

[56]  M. Aickin,et al.  Dose-related alpha-difluoromethylornithine ototoxicity. , 1991, American journal of clinical oncology.

[57]  P. Blackshear,et al.  Rat ornithine decarboxylase gene. Nucleotide sequence, potential regulatory elements, and comparison to the mouse gene. , 1989, The Journal of biological chemistry.

[58]  P. Fletcher,et al.  The polyamine synthesis inhibitor alpha-difluoromethylornithine is neuroprotective against N-methyl-D-aspartate-induced brain damage in vivo. , 1991, European journal of pharmacology.

[59]  M. Phillips,et al.  Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei. Implications for enzyme turnover and selective difluoromethylornithine inhibition. , 1987, The Journal of biological chemistry.

[60]  P. Loetscher,et al.  The C terminus of mouse ornithine decarboxylase confers rapid degradation on dihydrofolate reductase. Support for the pest hypothesis. , 1991, Journal of Biological Chemistry.

[61]  G. Kelloff,et al.  Chemoprevention of Colon Carcinogenesis by Dietary Administration of Piroxicam, α-Difluoromethylornithine, 16α-Fluoro-5-androsten-17-one, and Ellagic Acid Individually and in Combination , 1991 .

[62]  L. Ghoda,et al.  Prevention of rapid intracellular degradation of ODC by a carboxyl-terminal truncation. , 1989, Science.

[63]  R. Davis,et al.  Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA , 1992, Molecular and cellular biology.

[64]  R. Grady,et al.  Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia , 1990, Antimicrobial Agents and Chemotherapy.

[65]  J. Fike,et al.  Modification of Radiation-Induced Brain Injury by α-Difluoromethylornithine , 1991 .

[66]  Biochemical and morphological effects of polyamine biosynthesis inhibitors on Trichophyton and Microsporum. , 1991, Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology.

[67]  R. Pilz,et al.  Molecular and genetic characterization of an ornithine decarboxylase-deficient Chinese hamster cell line. , 1990, The Journal of biological chemistry.

[68]  E. Flescher,et al.  Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis. , 1989, The Journal of clinical investigation.

[69]  W. Brownell,et al.  An Animal Model of Hearing Loss From α-Difluoromethylornithine , 1989 .

[70]  C. Carter,et al.  Difluoromethyl ornithine protects against the neurotoxic effects of intrastriatally administered N-methyl-D-aspartate in vivo. , 1991, European journal of pharmacology.

[71]  C. Kahana,et al.  Nucleotide sequence of murine ornithine decarboxylase mRNA. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[72]  P. McCann,et al.  DL-a-Monofluoromethylputrescine is a potent irreversible inhibitor of Escherichia coli ornithine decarboxylase. , 1982, The Biochemical journal.

[73]  A. Pegg,et al.  Decarboxylation of alpha-difluoromethylornithine by ornithine decarboxylase. , 1987, The Biochemical journal.

[74]  A. Sjoerdsma,et al.  16 – Clinical Aspects of Inhibition of Ornithine Decarboxylase with Emphasis on Therapeutic Trials of Eflornithine (DFMO) in Cancer and Protozoan Diseases , 1987 .

[75]  W. Fonzi,et al.  The gene and the primary structure of ornithine decarboxylase from Saccharomyces cerevisiae. , 1987, The Journal of biological chemistry.

[76]  H. Koenig,et al.  Blood brain barrier breakdown in brain edema following cold injury is mediated by microvascular polyamines. , 1983, Biochemical and biophysical research communications.

[77]  N. Seiler.  Pharmacological properties of the natural polyamines and their depletion by biosynthesis inhibitors as a therapeutic approach. , 1991, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[78]  J. Seibold,et al.  Successful treatment of lupus nephritis in MRL-lpr/lpr mice by inhibiting ornithine decarboxylase. , 1991, Kidney international.

[79]  A. Bitonti,et al.  Catalytic irreversible inhibition of Trypanosoma brucei brucei ornithine decarboxylase by substrate and product analogs and their effects on murine trypanosomiasis. , 1985, Biochemical pharmacology.

[80]  C. Kahana,et al.  Mouse ornithine decarboxylase is phosphorylated by casein kinase-II at a predominant single location (serine 303). , 1991, European journal of biochemistry.

[81]  M. Prados,et al.  Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine. , 1989, Neurosurgery.

[82]  T. Bowlin,et al.  Methylacetylenic putrescine (MAP), an inhibitor of polyamine biosynthesis, prevents the development of collagen-induced arthritis. , 1990, Cellular immunology.

[83]  J. Ajani,et al.  Alterations in Polyamine Metabolism during Continuous Intravenous Infusion of α-Difluoromethylornithine Showing Correlation of Thrombocytopenia with α-Difluoromethylornithine Plasma Levels , 1989 .

[84]  Jennings Fw.  Chemotherapy of trypanosomiasis: the potentiation of antimonial compounds by difluoromethylornithine (DFMO). , 1991 .

[85]  M. McDermott,et al.  Polyamine accumulation and vasogenic oedema in the genesis of late delayed radiation injury of the central nervous system (CNS). , 1990, Acta neurochirurgica. Supplementum.

[86]  J. Sahai,et al.  Eflornithine for the Treatment of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome: A Preliminary Review , 1989, Pharmacotherapy.

[87]  E. Snell,et al.  Purification and properties of ornithine decarboxylase from Lactobacillus sp. 30a. , 1980, The Journal of biological chemistry.

[88]  P. McCann,et al.  Polyamine metabolism and function. , 1982, The American journal of physiology.

[89]  J. Shafer,et al.  D-serine dehydratase from Escherichia coli. DNA sequence and identification of catalytically inactive glycine to aspartic acid variants. , 1988, The Journal of biological chemistry.

[90]  Paul J. Seppanen,et al.  Complete amino acid sequence of human ornithine decarboxylase deduced from complementary DNA. , 1987, DNA.

[91]  R. Davey,et al.  Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia , 1990, Antimicrobial Agents and Chemotherapy.

[92]  K. Williams,et al.  Modulation of the NMDA receptor by polyamines. , 1991, Life sciences.

[93]  A. Galston,et al.  7 – Polyamine Metabolism , 1990 .

[94]  B. Wieringa,et al.  Cloning and nucleotide sequence of rat ornithine decarboxylase cDNA. , 1987, Gene.

[95]  R. Casero,et al.  The effects of DFMO on polyamine metabolism in the inner ear , 1991, Hearing Research.