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.
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Authors | B Woynarowska, H Wikiel, M Sharma, N Carpenter, G W Fleet, R J Bernacki |
Journal | Anticancer research
(Anticancer Res)
1992 Jan-Feb
Vol. 12
Issue 1
Pg. 161-6
ISSN: 0250-7005 [Print] Greece |
PMID | 1567163
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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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
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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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