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Polyamines as targets for therapeutic intervention

L J Marton1, A E Pegg

  • 1Department of Pathology, University of Wisconsin Medical School, Madison 53706, USA.

Annual Review of Pharmacology and Toxicology
|January 1, 1995
PubMed
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Compounds targeting polyamine pathways show therapeutic promise. Inhibitors and analogues offer potential treatments for parasitic diseases and cancer by disrupting cell growth.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cell Biology

Background:

  • Polyamines are vital cellular components crucial for organismal growth.
  • Dysregulation of polyamine metabolism is implicated in various diseases.
  • Therapeutic strategies targeting polyamine pathways are under investigation.

Purpose of the Study:

  • To explore the therapeutic potential of compounds interfering with polyamine biosynthesis and function.
  • To evaluate inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) for treating parasitic protozoan diseases and cancer.
  • To assess the utility of polyamine analogues in cancer therapy.

Main Methods:

  • Investigating the efficacy of ODC and SAMDC inhibitors.
  • Examining the antiproliferative activity of polyamine analogues.

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  • Considering the role of the polyamine-transport system in drug efficacy.

    • Main Results:

    • ODC inhibitors are effective against parasitic protozoa, such as in African sleeping sickness, and show potential as chemopreventive and antineoplastic agents.
    • SAMDC inhibitors also demonstrate potential for treating these diseases.
    • Certain polyamine analogues exhibit potent antiproliferative activity and are transported via the polyamine-transport system, suggesting therapeutic promise for cancer.

    Conclusions:

    • Compounds targeting polyamine metabolism, including ODC and SAMDC inhibitors, represent promising therapeutic agents for parasitic diseases and cancer.
    • Polyamine analogues with specific modifications show potent antiproliferative effects and may overcome resistance related to exogenous polyamine uptake.
    • Further research into polyamine pathway modulation and transport mechanisms is warranted for optimizing therapeutic strategies.