THE ROLE OF RAT SERUM CARBOXYLESTERASE IN THE ACTIVATION OF PACLITAXEL AND CAMPTOTHECIN PRODRUGS

Paclitaxel-2-ethylcarbonate (PC) is a prototype for a family of paclit axel prodrugs that have significant Levels of antitumor activities in rodent models for human cancer, In this study, an enzyme responsible f or the conversion of PC to paclitaxel was purified from rat serum, N-t erminal amino acid sequence analysis indicated that the isolated enzym e was rat serum carboxylesterase. This enzyme was shown to significant ly enhance the cytotoxic activities of both PC and 1-piperidino)-1-pip eridino]carbonyloxycamptothecin (CPT-11), a water-soluble analogue of camptothecin, on lung carcinoma and melanoma cell lines. Rat serum car boxylesterase may have applications for the site specific delivery of anticancer drugs to tumor masses.