Bowman-Birk inhibitors from legumes as colorectal chemopreventive agents

Table 3 Serine proteases as potential therapeutic targets of Bowman-Birk inhibitor-like proteins in pathological processes

Serine protease	Function	Pathological processes	Evidence of interaction with BBI-like proteins
Proteasome	Control of the turn-over of regulatory proteins involved in critical cellular processes including cell cycle progression, cell development and differentiation, apoptosis, angiogenesis and signaling pathways	Cancer, inflammatory processes, autoimmune diseases and aging	Soybean BBI specifically and potently inhibits the proteasomal chymotrypsin-like activity in vitro and in vivo in MCF7 cancer breast cells[76]
			Mice treated simultaneously with BBI and DMH show a significant decrease in the chymotrypsin- and trypsin-like proteasomal activity in comparison with those treated with DMH only[79]
			Soybean BBI suppress proteasomal chymotrypsin-like activity in U2OS human osteosarcoma cells in vitro[80]
Matriptase	Differentiation and function of epithelial tissues	Activator of critical molecules associated with tumor invasion and metastasis	SFTI-1, a cyclic peptide from sunflower having similar features to the trypsin inhibitory binding domain of BBI, is a very potent inhibitor (Ki: 0.92 nmol/L)[85]
			BBI from soybean and lima bean have been reported to inhibit matriptase activity in vitro[86]
Chymase	Key mediator in inflammatory cell signaling pathways	Inflammatory processes, allergic reactions and pulmonary fibrosis	Soybean BBI strongly inhibits chymase from rat mast cells (Ki: 13.2 nmol/L)[94]
			Soybean BBI is a highly effective inhibitor of human mast cell chymase, being not effective against human tryptase[88]
Cathepsin G	Degradation of extracellular matrix components, regulates inflammatory response and promotes apoptosis	Inflammatory processes, cancer and aging	Soybean BBI inhibits strongly cathepsin G (Ki: 1.2 nmol/L)[86]
Duodenase	Morphogenesis and tissue repair; inflammatory and mitogenic role; participation in activation cascade of digestive proteases	Inflammatory processes	Duodenase interacts specifically with the chymotrypsin inhibitory domain of soybean BBI (Ki: 4 nmol/L)[87]
Elastase	Degradation of extracellular matrix components	Pulmonary emphysema, cystic fibrosis, infections, inflammation and atherosclerosis	Soybean BBI inhibits hydrolysis of extracellular matrix components by leukocyte enzymes[95]
			Soybean BBI inhibit human leukocyte elastase (Ki: 2.3 nmol/L)[96]

BBI: Bowman-Birk inhibitor; DMH: Dimethylhydrazine; Ki: Constant of inhibition; SFTI-1: Sunflower trypsin inhibitor.