Inhibition of Oral Carcinogenesis by a Protease Inhibitor

The effect of the Bowman-Birk inhibitor (BBI) and soybean trypsin inhibitor (SBTI) on experimental 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced oral carcinogenesis in Syrian male hamsters was examined. All treatments were applied topically on both cheek pouches for 20 weeks, and the...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1986-03, Vol.76 (3), p.447-452
Main Authors: Messadi, D. V., Billings, P., Shklar, G., Kennedy, A. R.
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene
Animals
Cell Transformation, Neoplastic - drug effects
Cricetinae
Diethyl Pyrocarbonate - pharmacology
Iodoacetamide - pharmacology
Isoflurophate - pharmacology
Male
Mesocricetus
Mouth Neoplasms - enzymology
Mouth Neoplasms - pathology
Mouth Neoplasms - prevention & control
Peptide Hydrolases - analysis
Trypsin Inhibitor, Bowman-Birk Soybean - therapeutic use
Trypsin Inhibitors - pharmacology
Trypsin Inhibitors - therapeutic use
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Summary:The effect of the Bowman-Birk inhibitor (BBI) and soybean trypsin inhibitor (SBTI) on experimental 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced oral carcinogenesis in Syrian male hamsters was examined. All treatments were applied topically on both cheek pouches for 20 weeks, and the animals were then sacrificed. Gross and microscopic evaluations revealed a statistically significant reduction in the number of invasive carcinomas, the total number of tumors, and the tumor mass for the DMBA + BBI treatment group compared to animals treated with DMBA alone, DMBA and autoclaved BBI (a preparation in which protease inhibitor activity is destroyed), or DMBA + SBTI. A protease activity (with the use of Boc-Val-Pro-Arg-MCA as substrate) was measured and found to be elevated about tenfold in tumorous and nontumorous tissue from DMBA-treated cheek pouches. This protease activity was found to be decreased in the DMBA and BBI treatment group but not in the DMBA + SBTI or DMBA and autoclaved BBI treatment groups, as compared to the protease activity in the DMBA treatment group. Partial characterization of the Boc-Val-Pro-Arg-MCA hydrolyzing activity with diisopropyl fluorophosphate suggests that the proteolytic activity is a serine protease. lodoacetamide and diethyl pyrocarbonate also inhibit enzyme activity, suggesting that other residues may be necessary for catalysis, possibly including cysteine and histidine. Our results suggest that this protease activity may play a role in DMBA-induced cheek pouch carcinogenesis.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/76.3.447