title: The interaction of the potato-derived chymotrypsin inhibitor with C3H/10T1/2 cells.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: P C
authors.initials: PC
authors.lastname: Billings
authors.forename: T
authors.initials: T
authors.lastname: Jin
authors.forename: N
authors.initials: N
authors.lastname: Ohnishi
authors.forename: D C
authors.initials: DC
authors.lastname: Liao
authors.forename: J M
authors.initials: JM
authors.lastname: Habres
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D010940:Plant Proteins; D011480:Protease Inhibitors; C023578:proteinase inhibitor I (plants)