Suramin potently inhibits the enzymatic activity of PSM

Barbara S. Slusher, Carol W. Tiffany, Aviva Merion, Rena G. Lapidus, Paul F. Jackson

Research output: Contribution to journalArticlepeer-review


BACKGROUND. The polysulfonated napthlyurea suramin has shown significant antitumor activity in patients with hormone-refractory metastatic prostate cancer. The mechanism by which suramin exerts this effect is unknown. In 1993, prostate-specific membrane antigen (PSM) was identified as a prostate biomarker that is elevated in hormone-refractory and metastatic prostate cancer. PSM is a glutamate exocarboxypeptidase capable of cleaving the terminal alpha-linked glutamate from the dipeptide N-acetyl-aspartyl- glutamate (NAAG) and the gamma-linked glutamates from folate polyglutamate. METHODS. Using a NAAG hydrolytic radioenzymatic assay, we tested whether suramin had any effect on the enzymatic activity of PSM. RESULTS. We demonstrate that suramin potently inhibits the enzymatic activity of PSM with a K'i = 15 nM and 68 nM for the membrane-associated and soluble forms of PSM; respectively. In addition, we show that suramin inhibition of PSM enzyme activity displays the kinetics of a classic competitive inhibitor. CONCLUSIONS. This is one of the most potent activities described for suramin to date and may represent a portion of its pharmacologic and/or toxicological mechanism of action. (C) 2000 Wileys-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)55-60
Number of pages6
Issue number1
StatePublished - Jun 15 2000


  • Folate polyglutaniate
  • Glutamate
  • Glutamate carboxypeptidase
  • LNCaP cells
  • NAAG
  • NAALADase
  • PSM
  • Prostate cancer
  • Surarnin

ASJC Scopus subject areas

  • Oncology
  • Urology

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