Skip to main content
SpringerLink
Log in

Antitumor effect of methylglyoxal bis(3-aminopropyl-amidinohydrazone), a new inhibitor of S-adenosylmethionine and ornithine decarboxylases, on human erythroid leukemia K562 cells

  • Original Articles
  • Antitumor Effect, methyl Glyoxal bis(3-Aminopropylamidinohydrazone), Human Leukemia Cells, Ornithine Decarboxylase
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Methylglyoxal bis(3-aminopropylamidinohydrazone (MGBA) inhibited S-adenosylmethionine decarboxylase (AdoMetDC) activity competitively with S-adenosylmethionine (AdoMet), showing a Ki value of 2.60x10-5 M. It also inhibited ornithine decarboxylase competitively with ornithine, showing a Ki value of 3.80x10-5 M. MGBA inhibited the growth of human erythroid leukemia K562 cells. Putrescine, spermidine, and spermine concentrations in MGBA-treated cells were depressed to 19%, 36%, and 66% of the values of control cells, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

MGBA:

methylglyoxal bis(3-aminopropylamidinohydrazone)

AdoMetDC:

S-adenosylmethionine decarboxylase

AdoMet:

S-adenosylmethionine

ODC:

ornithine decarboxylase

References

  1. Alhonen-Hongisto L, Pösö H, Jänne J (1980) Inhibition by derivatives of diguanidines of cell proliferation in Ehrlich ascites cells grown in culture. Biochem J 188: 491

    Google Scholar 

  2. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248

    Google Scholar 

  3. Danzin C, Jung MJ, Claverie N, Grove J, Sjoerdsma A, Koch-Weser J (1979) Effects of α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on testosterone-induced regeneration of prostate and seminal vesicle in castrated rats. Biochem J 180: 507

    Google Scholar 

  4. Hibasami H, Tanaka M, Nagai J, Ikeda T (1980) Dicyclohexylamine, a potent inhibitor of spermidine synthase in mammalian cells. FEBS Lett 116: 99

    Google Scholar 

  5. Hibasami H, Tsukada T, Nakashima K (1985) Inhibition of tumor growth and metastasis by a spermidine synthase inhibitor, N-chlorosulfonyl-dicyclohexylamine. In: Imahori K, Suzuki F, Suzuki O, Bachrach U (eds) Polyamines: basic and clinical aspects. VNU Science Press, Utrecht, p 243

    Google Scholar 

  6. Hibasami H, Tsukada T, Maekawa S, Nakashima K (1986) Ornithine decarboxylase and spermidine/spermine N 1-acetyltransferase are induced in K562 cells by S-adenosylmethionine decarboxylase inhibitor methylglyoxal bis(guanylhydrazone) but not by analogous methylglyoxal bis(butylamidinohydrazone). Biochem Pharmacol 35: 4031

    Google Scholar 

  7. Jänne J, Pösö H, Raina A (1978) Polyamines in rapid growth and cancer. Biochim Biophys Acta 473: 241

    Google Scholar 

  8. Jänne J, Höltta E, Kallio A, Käpyaho K (1983) Role of polyamines and their antimetabolites in clinical medicine. Spec Top Endocrinol Metab 5: 227

    Google Scholar 

  9. Kremzner LT, Barrett RE, Terrano MJ (1970) Polyamine metabolism in the central and peripheral nervous system. Ann NY Acad Sci 171: 735

    Google Scholar 

  10. Maekawa S, Hibasami H, Tsukada T, Furusako S, Nakashima K, Yokoyama M (1986) Induction of spermidine/spermine N 1-acetyltransferase in needle-punctured rat lens as a model of traumatic cataract. Biochim Biophys Acta 883: 501

    Google Scholar 

  11. Mamont PS, Duchesne M-C, Grove J, Bey P (1978) Antiproliferative properties of DL-α-difluoromethylornithine in cultured cells. Biochem Biophys Res Commun 81: 58

    Google Scholar 

  12. Metcal BW, Bey P, Danzin C, Jung MJ, Casara P, Vevert JP (1978) Catalytic irreversible inhibition of mammalian ornithine decarboxylase by substrate and product analogous. J Am Chem Soc 100: 2551

    Google Scholar 

  13. Pegg AE, McGill SM (1978) Inhibition of diamine oxidase by 1,1-[(methylethanediylidene)-dinitrilo]-bis(3-aminoguanidine) and 1,1′-[methylethanediylidine)-dinitrilo]-diguanidine. Biochem Pharmacol 27: 1625

    Google Scholar 

  14. Pegg AE, Williams-Ashman HG (1969) On the role of S-adenosyl-L-methionine in the biosynthesis of spermidine by rat prostate. J Biol Chem 244: 682

    Google Scholar 

  15. Porter CW, Mikles-Robertson F, Kramer D, Dave C (1979) Correlation of ultrastructural and functional damage to mitochondria of ascites L1210 cells treated in vivo with methylglyoxal bis(guanylhydrazone) or ethydium bromide. Cancer Res 39: 2414

    Google Scholar 

  16. Pösö H, Jänne J (1976) Inhibition of polyamine accumulation and deoxyribonucleic acid synthesis in regenerating rat liver. Biochem J 158: 485

    Google Scholar 

  17. Pösö H, Pegg AE (1983) Measurement of the amount of ornithine decarboxylase in Saccharomyces cerevisiae and Saccharomyces uvarum by using α-[5-14C]difluoromethylornithine. Biochim Biophys Acta 747: 209

    Google Scholar 

  18. Rennert O, Miale T, Shukla J, Lawson D, Frias J (1976) Polyamine concentration in bovine marrow aspirates of children with leukemia and other malignancies. Blood 47: 695

    Google Scholar 

  19. Russell DH (1973) Polyamines in growth-normal and neoplastic. In: Russell DH (ed) Polyamines in normal and neoplastic growth. Raven Press, New York, p 1

    Google Scholar 

  20. Russell DH, Levy CC (1971) Polyamine accumulation and biosynthesis in a mouse L1210 leukemia. Cancer Res 31: 248

    Google Scholar 

  21. Seely JE, Pösö H, Pegg AE (1982) Purification of ornithine decarboxylase from kidneys of androgen-treated mice. Biochemistry 21: 3394

    Google Scholar 

  22. Williams-Ashman HG, Schenone A (1972) Methylglyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast-adenosylmethionine decarboxylases. Biochem Biophys Res Commun 46: 288

    Google Scholar 

  23. Williams-Ashman HG, Coppoc GL, Weber G (1972) Imbalance in ornithine metabolism in hepatomas of different growth rates as expressed in formation of putrescine, spermidine, and spermine. Cancer Res 32: 1924

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Mie University School of Medicine, 514, Tsu, Mie, Japan

    H. Hibasami, T. Tsukada, S. Maekawa, M. Sakurai & K. Nakashima

  2. Second Internal Medicine, Mie University School of Medicine, 514, Tsu, Mie, Japan

    S. Shirakawa

Authors
  1. H. Hibasami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Tsukada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Maekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Sakurai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Shirakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hibasami, H., Tsukada, T., Maekawa, S. et al. Antitumor effect of methylglyoxal bis(3-aminopropyl-amidinohydrazone), a new inhibitor of S-adenosylmethionine and ornithine decarboxylases, on human erythroid leukemia K562 cells. Cancer Chemother. Pharmacol. 22, 187–190 (1988). https://doi.org/10.1007/BF00273408

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00273408

Keywords

Search

Navigation