Some protease inhibitors are also inhibitors of poly(ADP-ribose) polymerase

• Published in: Carcinogenesis (New York) 1986-02, Vol.7 (2), p.323-325
• Main Authors: Cleaver, James E., Banda, Michael J., Troll, Walter, Borek, Carmia
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Antipain - pharmacology; Benzamides - pharmacology; Biological and medical sciences; Caffeine - pharmacology; Cell Transformation, Neoplastic - metabolism; Cells, Cultured; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Lymphocytes - enzymology; Methyl Methanesulfonate - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors; Protease Inhibitors - pharmacology; Transferases
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/7.2.323

The low-molecular-weight peptide protease inhibitors, tosyllysine-chloromethyl ketone, antipain and leupeptin, inhibited poly(ADP-ribose) [poly(ADP-Rib)] polymerase in permeable cells. The concentrations required for 50% inhibition were 3.6, 5 and 29 mM, respectively. Two peptides without protease inhibitor activity, fibrinopeptide A and phenylalanineleucine-(glutamine)2-leucine, also inhibited poly(ADP-Rib) synthesis; doses required for 50% inhibition were 0.37 and 11.2 mM, respectively. These concentrations lie within a range bracketed by the 50% inhibition concentrations of the strong and weak poly(ADP-Rib) synthesis inhibitors, 3-aminobenzamide (0.15 mM) and caffeine (> 100 mM), respectively. N-Ethylmaleimide also inhibited poly(ADP-Rib) synthesis, at a 50% inhibitory dose of 0.3 mM, in the absence of exogenous thiol reagents. High-molecular-weight protease inhibitors, such as soybean (including Bowman-Birk reagent) and lima bean trypsin inhibitors and human α1-protease inhibitor, had no effect on poly(ADP-Rib) synthesis up to 2 mg/ml. Interference with transformation and other cellular effects that have been reported in carcinogen-damaged cells treated with low-molecular-weight peptide protease inhibitors may therefore involve common mechanisms with poly(ADP-Rib) inhibitors. Similar effects of high-molecular-weight protease inhibitors presumably involve different mechanisms.