title: The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs.
abstract: Paclitaxel-2-ethylcarbonate (PC) is a prototype for a family of paclitaxel prodrugs that have significant levels of antitumor activities in rodent models for human cancer. In this study, an enzyme responsible for the conversion of PC to paclitaxel was purified from rat serum. N-terminal amino acid sequence analysis indicated that the isolated enzyme was rat serum carboxylesterase. This enzyme was shown to significantly enhance the cytotoxic activities of both PC and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a water-soluble analogue of camptothecin, on lung carcinoma and melanoma cell lines. Rat serum carboxylesterase may have applications for the site-specific delivery of anticancer drugs to tumor masses.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Senter
authors.forename: H
authors.initials: H
authors.lastname: Marquardt
authors.forename: B A
authors.initials: BA
authors.lastname: Thomas
authors.forename: B D
authors.initials: BD
authors.lastname: Hammock
authors.forename: I S
authors.initials: IS
authors.lastname: Frank
authors.forename: H P
authors.initials: HP
authors.lastname: Svensson
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D001711:Biotransformation; D002166:Camptothecin / Q000378:metabolism*; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000097:blood / Q000502:physiology*; D006801:Humans; D051379:Mice; D017239:Paclitaxel / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism*; D051381:Rats
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D017239:Paclitaxel; D002166:Camptothecin