A protein inhibitor of hepatic drug metabolizing enzymes from Ehrlich ascites cells

• Published in: Cancer letters Vol. 113; no. 1; pp. 1 - 8
• Main Author: Kamat, J.P.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 26.02.1997; Elsevier
• Subjects: Aminopyrine N-Demethylase - antagonists & inhibitors; Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Carcinoma, Ehrlich Tumor - enzymology; Carcinoma, Ehrlich Tumor - metabolism; Cytochrome P-450 Enzyme Inhibitors; Cytochromes b5 - antagonists & inhibitors; Ehrlich ascites; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Experimental digestive system and abdominal tumors; Female; Glucuronosyltransferase - antagonists & inhibitors; Inhibitor; Medical sciences; MFO; Mice; Microsomes, Liver - enzymology; Microsomes, Liver - metabolism; Mixed Function Oxygenases - antagonists & inhibitors; NADPH-Ferrihemoprotein Reductase - antagonists & inhibitors; Tumors; Ehrlich ascites; Inhibitor; MFO; Intraperitoneal administration; Purification; Enzyme; Isozyme; Cytochrome P450; Liver; Rodentia; Mixed function enzyme; Oxidase; Enzyme inhibitor; Microsome; Ehrlich ascite cell; In vitro; Vertebrata; Mammalia; Mouse; Animal; Ehrlich ascites tumor; Drug-metabolizing enzyme; Oxidoreductases
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(96)04536-3

Hepatic drug metabolizing enzymes were significantly decreased in Ehrlich ascites tumour-bearing mice. A protein inhibitor of hepatic drug metabolizing enzymes was isolated from Ehrlich ascites cells and purified. This involved ammonium sulphate fractionation (60–80%), DEAE, phosphocellulose, Sephadex G-100 and hydroxyapatite column chromatography. Purification attained was 800-fold. The inhibitory protein was effective in decreasing all the components of hepatic mixed-functionoxidase system and drug metabolizing enzymes both in vivo and in vitro. This novel inhibitor may have potential applications in chemical carcinogenesis.