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Inhibition of human ovarian carcinoma cell- and hexosaminidase- mediated degradation of extracellular matrix by sugar analogs.

Abstract
Human ovarian carcinoma (HOC) cell beta-N-acetylglucosaminidase (beta-NAG, EC 3.2.1.30) was found to be present in three isoenzymatic forms. All three forms were capable of degrading ECM. Therefore, inhibitors of beta-NAG were sought as potential anti-invasive agents. Two sugar analogs, 2-acetamido-2-deoxy-1,5-gluconolactone (CD80110) and 2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol (CD 86022), were evaluated for their ability to inhibit 1) human ovarian carcinoma beta-NAG isoenzyme activities, 2) degradation of radiolabeled ECM mediated by HOC cells and beta-NAG, and 3) cell growth. Both compounds were found to be competitive inhibitors of beta-NAG isoenzyme activities, with Ki values similar for all isoenzymes (2-8 microM). CD 80110 and CD 86022 inhibited HOC cell-mediated degradation of [3H]glucosamine labeled ECM without notable effect on cell growth. Enzyme-mediated degradation of ECM was also inhibited by both sugar analogs. Analysis of degradation products after cell- or enzyme-mediated digestion of ECM revealed a decrease in the amount of both free aminosugars and high molecular material caused by inhibitors. These results support a role for beta-NAG in degradation of extracellular matrix components and suggest the usefulness of hexosaminidase inhibitors as potential antiinvasive agents.
AuthorsB Woynarowska, H Wikiel, M Sharma, N Carpenter, G W Fleet, R J Bernacki
JournalAnticancer research (Anticancer Res) 1992 Jan-Feb Vol. 12 Issue 1 Pg. 161-6 ISSN: 0250-7005 [Print] Greece
PMID1567163 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Carbohydrates
  • Isoenzymes
  • Piperidines
  • 2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol
  • 2-acetamido-2-deoxy-D-glucono-(1,5)-lactone
  • 1-Deoxynojirimycin
  • Acetylglucosaminidase
  • Acetylglucosamine
Topics
  • 1-Deoxynojirimycin (analogs & derivatives)
  • Acetylglucosamine (analogs & derivatives, pharmacology)
  • Acetylglucosaminidase (analysis, antagonists & inhibitors)
  • Carbohydrates (pharmacology)
  • Extracellular Matrix (metabolism)
  • Female
  • Humans
  • Isoenzymes (analysis)
  • Neoplasm Invasiveness
  • Ovarian Neoplasms (enzymology)
  • Piperidines (pharmacology)
  • Tumor Cells, Cultured

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