Bowman-Birk inhibitors from legumes as colorectal chemopreventive agents

Abstract

Aberrant functioning of serine proteases in inflammatory and carcinogenic processes within the gastrointestinal tract (GIT) has prompted scientists to investigate the potential of serine protease inhibitors, both natural and synthetic, as modulators of their proteolytic activities. Protease inhibitors of the Bowman-Birk type, a major protease inhibitor family in legume seeds, which inhibit potently and specifically trypsin- and chymotrypsin-like proteases, are currently being investigated as colorectal chemopreventive agents. Physiologically relevant amounts of Bowman-Birk inhibitors (BBI) can reach the large intestine in active form due to their extraordinary resistance to extreme conditions within the GIT. Studies in animal models have proven that dietary BBI from several legume sources, including soybean, pea, lentil and chickpea, can prevent or suppress carcinogenic and inflammatory processes within the GIT. Although the therapeutic targets and the action mechanism of BBI have not yet been elucidated, the emerging evidence suggests that BBI exert their preventive properties via protease inhibition; in this sense, serine proteases should be considered as primary targets in early stages of carcinogenesis. The validation of candidate serine proteases as therapeutic targets together with the identification, within the wide array of natural BBI variants, of the most potent and specific protease inhibitors, are necessary to better understand the potential of this protein family as colorectal chemopreventive agents.

Keywords: Bowman-Birk inhibitors; Cell proliferation; Chemoprevention; Colorectal cancer; Legumes; Serine proteases

Core tip: Bowman-Birk inhibitors (BBI) from legumes, such as soybean, pea, lentil and chickpea, are a class of naturally-occurring serine protease inhibitors with potential anti-inflammatory and chemopreventive properties within the gastrointestinal tract (GIT). BBI are extensively disulphide-linked within proteins and have been demonstrated to be structurally and functionally resistant to the challenges of the GIT in vivo. Recent data suggest that trypsin- and chymotrypsin-like proteases involved in early stages of carcinogenesis should be primary targets in investigating the potential of BBI as colorectal chemopreventive agents; so far, the therapeutic targets as well as action mechanism of BBI remain unknown.