The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs

Peter D. Senter, Hans Marquardt, Beth A. Thomas, Bruce D. Hammock, Ian S. Frank, Håkan P. Svensson

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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.

Original languageEnglish (US)
Pages (from-to)1471-1474
Number of pages4
JournalCancer Research
Volume56
Issue number7
StatePublished - Apr 1 1996

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Senter, P. D., Marquardt, H., Thomas, B. A., Hammock, B. D., Frank, I. S., & Svensson, H. P. (1996). The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs. Cancer Research, 56(7), 1471-1474.