Biological Effects of Acetomycin. II. Inactivation by Esterases in Vitro

Acetomycin has antitumor activity in vitro but not in vivo. HCT-8 human colon adenocarcinoma assays in the presence of a drug metabolizing system (rat liver S9 fraction) demonstrated that liver enzymes inactivated acetomycin. The structure of acetomycin suggested that an esterase could be the key inactivating enzyme. Assays with porcine liver esterase (EC 3.1.1.1) showed that this enzyme rapidly abolishes the activity of acetomycin against HCT-8 cells. The potential utility of acetomycin as an antitumor agent thus depends on finding a means of preventing esterase inactivation.