Inhibition of radiation-induced transformation of C3H/10T1/2 cells by carboxypeptidase inhibitor 1 and inhibitor II from potatoes.
In the current study, the ability of four protease inhibitors to suppress radiation-induced transformation of C3H/10T1/2 cells was investigated. The inhibitors tested included: (i) aprotinin (a serine protease inhibitor), (ii) N-acetyl-L-tyrosine ethyl ester (a chymotrypsin substrate and competitive inhibitor of protein degradation), (iii) carboxypeptidase inhibitor (a metallo-exopeptidase inhibitor) and (iv) Inhibitor II (a chymotrypsin/trypsin inhibitor). While none of the inhibitors were toxic to the cells at the concentrations employed, only carboxypeptidase inhibitor and inhibitor II are internalized radiation-induced transformation in a statistically significant manner. Utilizing fluorescent labeled inhibitors, we found that carboxypeptidase inhibitors and Inhibitor II are internalized by the cells. Fluorescent-labeled inhibitor could be observed in the cells within 15 min of incubation and is present in distinct intercellular vacuoles within 1 h. These results indicate that carboxypeptidase inhibitor and Inhibitor II are internalized by C3H/10T1/2 cells and thus would be able to inhibit intracellular proteases (or other enzymes) involved in the conversion of a cell to the malignant state.
Billings
P C
PC
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Morrow
A R
AR
Ryan
C A
CA
Kennedy
A R
AR
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D051379:Mice; D008809:Mice, Inbred C3H; D010940:Plant Proteins / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D010940:Plant Proteins; D011480:Protease Inhibitors; D014443:Tyrosine; C007651:ethyl N-alpha-acetyl-tyrosinate; D007611:Aprotinin; D002268:Carboxypeptidases