Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protease inhibitors have been shown to be effective suppressors of carcinogenesis in vitro and in vivo. For example, the soybean-derived Bowman-Birk inhibitor (BBI) suppresses dimethylhydrazine-induced colon carcinogenesis in mice. Relatively little is known about the effects of protease inhibitors on intestinal epithelial cells. In the present study, we have investigated the interaction of the anticarcinogenic BBI with intestinal epithelial cells. At the concentrations examined, BBI was non-toxic and had no effect on the doubling time, saturation density or rate of DNA synthesis by these cells. This compound was taken up by these cells in a time dependent manner and was present in the cells for 12 h following a 2 h incubation with BBI. Subcellular fractionation experiments demonstrated that the bulk of the internalised inhibitor was present in the cytosol. Analysis of BBI from treated cells on a chymotrypsin affinity column revealed that active inhibitor was present in the cells. Our results indicate that the BBI is internalised by colonic epithelial cells which would allow BBI to inhibit critical intracellular proteases and thus suppress malignant transformation.
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PMID:Internalisation of the Bowman-Birk protease inhibitor by intestinal epithelial cells. 183 26

Trypsin inhibitor (TI) occurs naturally in many foods from plants, notably soybean protein products. Heat treatment inactivates TI and improves nutritional quality, but residual TI activity of 5 to 20% remains after typical commercial treatments. Chronic feeding of TI or products that contain TI can inhibit trypsin and chymotrypsin, stimulate their secretion, cause hypertrophy and hyperplasia of the pancreas, and lead to adenomas and carcinomas of the exocrine pancreas. In the rat, TI promotes pancreatic carcinogenesis initiated by azaserine. Data needed for possible risk assessment on TI would include 2-year bioassays from animals treated with TI and fed diets carefully controlled for type and amount of fat (which also promotes pancreatic carcinogenesis). The effects of TI on protein nutrition would have to be considered when identifying the maximum tolerated dose. Major reductions in human dietary TI exposure may not be feasible because of the multiple sources of TI, the substantial promotion by other factors such as fat, and the adverse effects of excessive heat on food products. For risk assessment of TI in a particular food, other promotors and the feasibility of decreasing TI intake must be considered.
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PMID:Residue trypsin inhibitor: data needs for risk assessment. 189 96

Protease inhibitors have been shown to be effective suppressors of carcinogenesis in vitro and in vivo. For example, the potato-derived chymotrypsin inhibitor 1 (CI-1) suppresses radiation transformation of C3H/10T1/2 cells in vitro. In the current study, we have investigated the interaction of CI-1 with C3H/10T1/2 cells. At the concentrations examined, CI-1 was non-toxic and had no effect on the doubling time or saturation density of these cells. This compound was taken up by these cells in a time dependent manner. Analysis of CI-1 from treated cells on a chymotrypsin affinity column revealed that active inhibitor was present in the cells. Additionally, CI-1, as well as the soybean derived Bowman-Birk inhibitor and chymostatin, blocked the cleavage of the peptide substrate Suc-Ala-Ala-Pro-Phe-MCA by intact C3H/10T1/2 cells. We have previously demonstrated that this substrate will reduce the transformation yield following treatment of cells with ionizing radiation. Our results suggest that CI-1 may inhibit transformation of C3H/10T1/2 cells in vitro by inhibiting the activity of Suc-Ala-Ala-Pro-Phe-MCA hydrolyzing activity in these cells.
Carcinogenesis 1991 Apr
PMID:The interaction of the potato-derived chymotrypsin inhibitor with C3H/10T1/2 cells. 201 29

The Bowman-Birk protease inhibitor (BBI) is a legume-derived inhibitor of chymotrypsin and trypsin that has been shown to suppress cellular transformation and tumorigenesis. In the present investigation the effects of various BBI administration schedules were evaluated for suppression of 3-methylcholanthrene (3-MCA)-induced transformation of C3H/10T1/2 cells. At a concentration of 30 micrograms/ml, BBI demonstrated no toxicity to C3H/10T1/2 cells treated with 3-MCA. However, transformation of C3H/10T1/2 cells was significantly reduced when BBI was added to the cultures for a period of 14 or 42 days, starting immediately after exposure to the carcinogen. When BBI was administered only during the time of carcinogen exposure or alternatively beginning on day 15 and then continuously throughout the remainder of the 6-week transformation assay, it was ineffective for suppressing 3-MCA-induced cellular transformation. These findings indicate that BBI exerts its chemopreventive effect during the early stage of chemical carcinogen-induced cellular transformation.
Carcinogenesis 1991 May
PMID:Suppression of 3-methylcholanthrene-induced cellular transformation by timed administration of the Bowman-Birk protease inhibitor. 202 60

A large body of experimental work has revealed that protease inhibitors (PI) are highly effective suppressors of carcinogenesis. Little is known about the level of PI activity in the diet of the US population. In the present study, we assayed the levels of PI activity in dietary samples from 31 free-living subjects who saved duplicate portions of all foods consumed over two 24-hour periods, six months apart. The majority of samples (90%) contained detectable PI activity; 82% contained trypsin inhibitory activity; 61% contained chymotrypsin inhibitory activity. Of those samples containing chymotrypsin inhibitory activity, 87% also contained trypsin inhibitory activity. The median concentration of soluble chymotrypsin inhibitory activity present in these samples was 6.5 micrograms/g food (range 0-150 micrograms/g food), whereas the median concentration of soluble trypsin inhibitory activity was 14.5 micrograms/g food (range 0-465 micrograms/g food). We conclude that a) human diet samples contain both chymotrypsin and trypsin inhibitory activity, b) the levels of PI in some of these samples was similar to that found to be anticarcinogenic in animal studies, and c) due to the large within-subject variation in PI intake, assessment of long-term dietary intake in epidemiological studies will be necessary to accurately classify subjects according to PI intake.
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PMID:Protease inhibitor content of human dietary samples. 221 1

In the present study, we examined the ability of chymostatin, a highly specific inhibitor of chymotrypsin, to suppress dimethylhydrazine-induced colon carcinogenesis, and the dose-response relationship for an extract of soybeans containing the Bowman-Birk inhibitor (BBI) to suppress dimethylhydrazine-induced colon carcinogenesis, when added to the diet of mice. Our results showed that: (i) diets containing 0.1% BBI reduced the incidence of adenocarcinomas of the colon approximately 50%, but had no effect on the incidence of squamous cell carcinomas of the anal gland; (ii) the suppressive effect requires protease inhibitor activity, as the autoclaved BBI, in which all protease inhibitory activity has been destroyed, was ineffective at suppressing the incidence of adenocarcinomas; (iii) chymostatin suppressed the incidence of squamous cell carcinomas of the anal gland, but not adenocarcinomas of the colon; and (iv) the growth rates of the animals were the same in each of the experimental groups. Our results indicate that the levels of anticarcinogenic protease inhibitors present in the diets of these animals do not have any adverse effects on the growth or general health of the animals.
Carcinogenesis 1990 Jul
PMID:Protease inhibitor suppression of colon and anal gland carcinogenesis induced by dimethylhydrazine. 237 68

In the current studies, we have examined the effect of two specific protease substrates, the thrombin substrate Boc-Val-Pro-Arg-MCA and the chymotrypsin substrate Suc-Ala-Ala-Pro-Phe-MCA, on the oncogenic transformation of C3H/10T1/2 cells induced with: (i) 6 Gy of X-radiation and (ii) 4 Gy of X-radiation followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Both substrates reduced radiation transformation while only Suc-Ala-Ala-Pro-Phe-MCA suppressed the TPA enhancement of radiation transformation. We have previously reported that C3H/10T1/2 cells contain at least two proteolytic activities which will cleave these substrates. Our results therefore suggest that: (i) these substrates may inhibit oncogenic transformation due to the fact that they are competitive substrates for these enzymes; and (ii) two or more proteases play an important role in the malignant transformation of these cells.
Carcinogenesis 1990 Feb
PMID:Inhibition of radiation-induced transformation of C3H/10T1/2 cells by specific protease substrates. 240 34

This investigation sought to characterize biochemically the tumor-specific transplantation antigens (TSTA) expressed on the cell surface of a panel of chemically induced fibrosarcomas of C3H/HeJ mice. Results suggest a uniform antigenic framework upon which individual specificities are superimposed. The antigens expressed by the 3-methylcholanthrene-induced fibrosarcomas MCA-D, MCA-F, and MCA-2A fulfill the requirements of a TSTA; namely, immunization of syngeneic hosts with irradiated cells or soluble extracts engenders a tumor-specific immune response such that animals resist challenge with the same, but not another, tumor. Brief incubation of intact tumor cells in single-phase aqueous solutions of 2.5% (v/v) 1-butanol extracts an immunoprotective TSTA, but not alloantigenic activity, from MCA-F cells. This extraction protocol was extended to the two other MCA-induced neoplasms. The butanol-extracted TSTA from the three tumors displayed isoelectric pHs of 6.4 to 6.6 following preparative isoelectric focusing. The tumor-specific immunoprotective activity from all three tumors displayed an apparent molecular weight of 150,000 (150 kDa) during high-performance gel permeation chromatography. The chromatographic properties of the 150 kDa antigens were unaffected by reduction using dithiothreitol, but incubation in acetate buffer, pH 3.0, dissociated the 150 kDa complex into at least two components with molecular weights of 70 to 100 kDa and 20 to 40 kDa. Only the smaller component displayed TSTA activity. The presence of two major components in the 150-kDa antigen was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TSTA activity was sensitive to digestion with pronase, papain, chymotrypsin, and alpha-mannosidase, but resistant to DNase, RNase, neuraminidase, trypsin, endoglycosidase H, and a mixed-function glycosidase. In addition, the TSTA activity was unaffected by heating. These data demonstrate that MCA carcinogenesis results in the expression of immunologically unique epitopes on biochemically related glycoproteins and suggest a unified mechanism for the generation of TSTA polymorphism.
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PMID:Biochemical characterization of 1-butanol-extracted murine tumor-specific transplantation antigens. 240 45

In the current study, the ability of four protease inhibitors to suppress radiation-induced transformation of C3H/10T1/2 cells was investigated. The inhibitors tested included: (i) aprotinin (a serine protease inhibitor), (ii) N-acetyl-L-tyrosine ethyl ester (a chymotrypsin substrate and competitive inhibitor of protein degradation), (iii) carboxypeptidase inhibitor (a metallo-exopeptidase inhibitor) and (iv) Inhibitor II (a chymotrypsin/trypsin inhibitor). While none of the inhibitors were toxic to the cells at the concentrations employed, only carboxypeptidase inhibitor and inhibitor II are internalized radiation-induced transformation in a statistically significant manner. Utilizing fluorescent labeled inhibitors, we found that carboxypeptidase inhibitors and Inhibitor II are internalized by the cells. Fluorescent-labeled inhibitor could be observed in the cells within 15 min of incubation and is present in distinct intercellular vacuoles within 1 h. These results indicate that carboxypeptidase inhibitor and Inhibitor II are internalized by C3H/10T1/2 cells and thus would be able to inhibit intracellular proteases (or other enzymes) involved in the conversion of a cell to the malignant state.
Carcinogenesis 1989 Apr
PMID:Inhibition of radiation-induced transformation of C3H/10T1/2 cells by carboxypeptidase inhibitor 1 and inhibitor II from potatoes. 246 57

In this report, we have investigated whether a protease inhibitor obtained from potatoes (chymotrypsin inhibitor 1; CI-1) will inhibit carcinogen-induced transformation of C3H/10T1/2 cells. CI-1 was as effective as the soybean-derived Bowman Birk inhibitor at suppressing radiation-induced transformation of C3H/10T1/2 cells, at a concentration of 10 micrograms/ml. The inhibitor was not toxic to the cells at concentrations of 0.1-10 micrograms/ml, the concentrations of CI-1 employed in the transformation experiments. To investigate the interaction of this inhibitor with the target cells, binding studies were carried out. 125I-labelled CI-1 could not be displaced from C3H/10T1/2 cells by co-incubation of the cells with a 5000-fold excess of unlabelled inhibitor. These results suggest that this inhibitor does not reversibly bind to specific receptor proteins on the surface of these cells.
Carcinogenesis 1987 Jun
PMID:Inhibition of radiation-induced transformation of C3H/10T1/2 cells by chymotrypsin inhibitor 1 from potatoes. 360 78


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