Internalisation of the Bowman-Birk protease inhibitor by intestinal epithelial cells

Billings, Paul C.; Brandon, David L.; Habres, Joan M.

doi:10.1016/0277-5379(91)90144-3

Cited by 34 publications

(11 citation statements)

References 16 publications

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“…Chymase, a key mediator in inflammatory cell signalling pathways, is a chymotrypsin-like serine protease, which is stored primarily in mast cell granules and released upon degranulation, and has been reported to be susceptible to inhibition by soybean BBI [18]. It has also been suggested that BBI internalisation by epithelial cells could facilitate the inhibition of intracellular target proteases associated with the transformation of normal to malignant cells [12]. Proteasomes are involved in control of the cell cycle by proteolytic degradation of several cell cycle regulatory proteins such as cyclins and cyclin-dependent kinases and thus represent a promising target structure for early anticancer strategies in combination with cytotoxic drugs [41].…”

Section: Discussionmentioning

confidence: 98%

“…A soybean Bowman-Birk inhibitor concentrate (BBIC), an extract enriched in BBI, exerted a protective effect in dimethylhydrazine-treated animals, reducing the incidence and frequency of colon tumours in mice [11,12] and rats [3]. In these studies, adverse side effects of BBIC were not documented for either animal growth or organ physiology.…”

Section: Introductionmentioning

confidence: 97%

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The cytotoxic effect of Bowman–Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases

Clemente

Moreno

Marín-Manzano

et al. 2010

Molecular Nutrition Food Res

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Bowman-Birk inhibitors (BBI) from soybean and related proteins are naturally occurring protease inhibitors with potential health-promoting properties within the gastrointestinal tract. In this work, we have investigated the effects of soybean BBI proteins on HT29 colon adenocarcinoma cells, compared with non-malignant colonic fibroblast CCD-18Co cells. Two major soybean isoinhibitors, IBB1 and IBBD2, showing considerable amino acid sequence divergence within their inhibitory domains, were purified in order to examine their functional properties, including their individual effects on the proliferation of HT29 colon cancer cells. IBB1 inhibited both trypsin and chymotrypsin whereas IBBD2 inhibited trypsin only. Despite showing significant differences in their enzyme inhibitory properties, the median inhibitory concentration values determined for IBB1 and IBBD2 on HT29 cell growth were not significantly different (39.9+/-2.3 and 48.3+/-3.5 microM, respectively). The cell cycle distribution pattern of HT29 colon cancer cells was affected by BBI treatment in a dose-dependent manner, with cells becoming blocked in the G0-G1 phase. Chemically inactive soybean BBI had a weak but non-significant effect on the proliferation of HT29 cells. The anti-proliferative properties of BBI isoinhibitors from soybean reveal that both trypsin- and chymotrypsin-like proteases involved in carcinogenesis should be considered as potential targets of BBI-like proteins.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

The cytotoxic effect of Bowman–Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases

Clemente

Moreno

Marín-Manzano

et al. 2010

Molecular Nutrition Food Res

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“…It is thought that this tightly disulfidebonded structure contributes to the high stability of BBI, which can withstand boiling temperatures without losing activity and can survive transit through the digestive tract [22,23]. Studies performed with radiolabeled BBI indicate that approximately one half of the BBI administered orally is eliminated in the feces in an unaltered form, while the rest enters intestinal epithelial cells [24] or crosses the intestinal epithelium via a paracellular mechanism [22]. Three hours after oral administration, [ 125 I]BBI is present in all major organs except the brain [22].…”

Section: Discussionmentioning

confidence: 99%

Bowman-Birk Inhibitor Concentrate: A Novel Therapeutic Agent for Patients with Active Ulcerative Colitis

et al. 2007

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Bowman-Birk inhibitor concentrate (BBIC), a soy extract with high protease inhibitor activity, is efficacious in the treatment of colitis in mice and has been used in numerous clinical trials. A randomized, double blind, placebo-controlled trial was performed to investigate the safety and possible benefits of BBIC in patients with active ulcerative colitis. The Sutherland Disease Activity Index (SDAI) was used to assess disease activity, response (Index decrease > or = 3), and remission (Index < or = 1 with no rectal bleeding) in patients receiving 12 weeks of therapy. The Index scores of patients receiving BBIC decreased more than those of the patients receiving placebo (P = 0.067). Beneficial trends were observed in the rates of remission (P = 0.082) and clinical response (P = 0.22). No severe adverse events were observed. This trial suggests a potential benefit over placebo for both achieving clinical response and induction of remission in patients with active ulcerative colitis without apparent toxicity.

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“…These studies indicated that approximately half of the BBI administered orally is excreted in the feces in an unaltered form, whereas the remainder enters intestinal epithelial cells (25) or crosses the intestinal lumen via a paracellular mechanism (26). In animal studies, BBI is able to survive the digestive process, reach the colon in an active form and is capable of interacting with proteases in the same manner as expected for BBI (26,27).…”

Section: Discussionmentioning

confidence: 99%

Phase I randomized double-blind placebo-controlled single-dose safety studies of Bowman-Birk inhibitor concentrate

et al. 2014

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In previously performed animal studies and Phase I–II human trials, Bowman-Birk inhibitor concentrate (BBIC) appeared to be a promising cancer chemopreventive agent. The present study describes the results of two phase I randomized double-blind placebo-controlled trials performed in male subjects to assess the safety and toxicity of the original and new formulations of BBIC administered in a single dose as a suspension in orange juice. The dose of BBIC varied from 800–2,000 chymotrypsin inhibitor (CI) units. The BBI concentration in the serum samples collected from the subjects was analyzed by a dot-blot analysis procedure using the 5G2 monoclonal antibody, which is specific for reduced BBI. A total of 41 subjects were enrolled, 20 in the initial BBIC study and 21 in the second BBIC study. In these human trials, no clinically relevant changes in hematological or biochemical parameters were observed. Overall, BBIC was found to be well-tolerated. For these BBIC single-dose phase I trials, there was no dose-limiting toxicity for BBIC, even at the highest dose evaluated, and there were no apparent differences between the clinical trial results for the two formulations of BBIC. The bioavailability of BBI in the second clinical trial, which used the new BBIC formulation, was approximately 40 to 43% of the BBI bioavailability reached in the first clinical trial, which used the original BBIC formulation. The observed bioavailability difference was attributed to the different BBIC formulations used in these two clinical trials. These trials demonstrated that BBIC is safe when administered in a single dose of up to 2,000 CI units. Therefore, the results from the two trials indicate that a multi-dose trial of BBIC may be safely performed with doses of up to 2,000 CI units per day.

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Internalisation of the Bowman-Birk protease inhibitor by intestinal epithelial cells

Cited by 34 publications

References 16 publications

The cytotoxic effect of Bowman–Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases

The cytotoxic effect of Bowman–Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases

Bowman-Birk Inhibitor Concentrate: A Novel Therapeutic Agent for Patients with Active Ulcerative Colitis

Phase I randomized double-blind placebo-controlled single-dose safety studies of Bowman-Birk inhibitor concentrate

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