title: Pea (Pisum sativum L.) protease inhibitors from the Bowman-Birk class influence the growth of human colorectal adenocarcinoma HT29 cells in vitro.
abstract: The Bowman-Birk trypsin-chymotrypsin inhibitor (BBI) from soybean has been described as a potential cancer chemopreventive agent. We have compared the effects of BBI with those of two variant recombinant pea (Pisum sativum L.) seed protease inhibitors, rTI1B and rTI2B, homologous to BBI but differing in inhibitory activity, on the growth of human colorectal adenocarcinoma HT29 cells in vitro. A significant and dose-dependent decrease in the growth of HT29 cells was observed using all protease inhibitors, with rTI1B showing the largest decrease (IC50 = 46 microM). Inclusion of the pan-caspase inhibitor, Boc-D-FMK, did not negate the effects of rTI1B or rTI2B in the cell assays. The relative effectiveness of rTI1B and rTI2B may correlate with a variant amino acid sequence within their respective chymotrypsin inhibitory domain, in agreement with a chymotrypsin-like protease as a potential target.
authors.affiliation: Department of Metabolic Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom. alfonso.clemente@eez.csi.es
authors.forename: Alfonso
authors.initials: A
authors.lastname: Clemente
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Gee
authors.forename: Ian T
authors.initials: IT
authors.lastname: Johnson
authors.forename: Donald A
authors.initials: DA
authors.lastname: Mackenzie
authors.forename: Claire
authors.initials: C
authors.lastname: Domoney
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000595:Amino Acid Sequence; D002455:Cell Division / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D008969:Molecular Sequence Data; D018532:Pisum sativum / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology
chemical_list: D010940:Plant Proteins; D011480:Protease Inhibitors; D011994:Recombinant Proteins; C575990:TI1B protein, Pisum sativa; D014358:Trypsin Inhibitor, Bowman-Birk Soybean