Non-Selective Inhibition of Transformed Cell Growth by a Protease Inhibitor
The protease inhibitors N-tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N-tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to selectively inhibit growth of simian virus 40-transformed cells, suggesting that proteolytic enzymes play a role in loss of cellular growth control fol...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 71; no. 5; pp. 1748 - 1752 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences of the United States of America
01.05.1974
National Acad Sciences |
Subjects | |
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Abstract | The protease inhibitors N-tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N-tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to selectively inhibit growth of simian virus 40-transformed cells, suggesting that proteolytic enzymes play a role in loss of cellular growth control following viral transformation. In contrast, this study shows that TPCK-mediated growth inhibition is non-selective, since the growth of both simian virus 40-transformed and untransformed 3T3 cells is similarly reduced by TPCK treatment. Under certain conditions, TPCK treatment of simian virus 40-transformed cells yields a reversible ``growth plateau'' condition which mimics, but is not equivalent to, contact inhibition of growth. The growth inhibitory effects of TPCK are due to inhibition of protein synthesis, since TPCK treatment resulted in a diminution of protein synthesis and since the ``growth plateau'' effect was also observed in cultures treated with cycloheximide. |
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AbstractList | The protease inhibitors N-tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N-tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to selectively inhibit growth of simian virus 40-transformed cells, suggesting that proteolytic enzymes play a role in loss of cellular growth control following viral transformation. In contrast, this study shows that TPCK-mediated growth inhibition is non-selective, since the growth of both simian virus 40-transformed and untransformed 3T3 cells is similarly reduced by TPCK treatment. Under certain conditions, TPCK treatment of simian virus 40-transformed cells yields a reversible ``growth plateau'' condition which mimics, but is not equivalent to, contact inhibition of growth. The growth inhibitory effects of TPCK are due to inhibition of protein synthesis, since TPCK treatment resulted in a diminution of protein synthesis and since the ``growth plateau'' effect was also observed in cultures treated with cycloheximide. The protease inhibitors N -tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N -tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to selectively inhibit growth of simian virus 40-transformed cells, suggesting that proteolytic enzymes play a role in loss of cellular growth control following viral transformation. In contrast, this study shows that TPCK-mediated growth inhibition is non-selective, since the growth of both simian virus 40-transformed and untransformed 3T3 cells is similarly reduced by TPCK treatment. Under certain conditions, TPCK treatment of simian virus 40-transformed cells yields a reversible “growth plateau” condition which mimics, but is not equivalent to, contact inhibition of growth. The growth inhibitory effects of TPCK are due to inhibition of protein synthesis, since TPCK treatment resulted in a diminution of protein synthesis and since the “growth plateau” effect was also observed in cultures treated with cycloheximide. The protease inhibitors N -tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N -tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to selectively inhibit growth of simian virus 40-transformed cells, suggesting that proteolytic enzymes play a role in loss of cellular growth control following viral transformation. In contrast, this study shows that TPCK-mediated growth inhibition is non-selective, since the growth of both simian virus 40-transformed and untransformed 3T3 cells is similarly reduced by TPCK treatment. Under certain conditions, TPCK treatment of simian virus 40-transformed cells yields a reversible “growth plateau” condition which mimics, but is not equivalent to, contact inhibition of growth. The growth inhibitory effects of TPCK are due to inhibition of protein synthesis, since TPCK treatment resulted in a diminution of protein synthesis and since the “growth plateau” effect was also observed in cultures treated with cycloheximide. contact inhibition 3T3 cells simian virus 40 transformation N-tosyl-L-phenylalanylchloromethyl ketone |
Author | Black, Paul H. Chou, Iih-Nan Roblin, Richard O. |
AuthorAffiliation | Department of Medicine, Boston, Mass. 02114 Department of Molecular Genetics, Harvard Medical School, Boston, Mass. 02114 Department of Infectious Disease Unit, Massachusetts General Hospital, Boston, Mass. 02114 Department of Microbiology, Boston, Mass. 02114 |
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Snippet | The protease inhibitors N-tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N-tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to... The protease inhibitors N -tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N -tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to... The protease inhibitors N -tosyl-L-phenylalanylchloromethyl ketone (TPCK) and N -tosyl-L-lysylchloromethyl ketone (TLCK) have previously been shown to... |
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SubjectTerms | 3T3 cells Amino Acids - metabolism Biological Sciences: Cell Biology Cell culture techniques Cell Division - drug effects Cell growth Cell Line Cell lines Cells Chlorine - pharmacology Clone Cells Contact Inhibition Cultured cells Depression, Chemical DNA - biosynthesis HeLa cells Lysine - pharmacology Peptide Hydrolases - physiology Phenylalanine - pharmacology Protease Inhibitors Protein Biosynthesis Protein synthesis Simian virus 40 Swiss 3T3 cells Thymidine - metabolism Tosyl Compounds - pharmacology Tritium |
Title | Non-Selective Inhibition of Transformed Cell Growth by a Protease Inhibitor |
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