CPT-11 converting carboxylesterase and topoisomerase activities in tumour and normal colon and liver tissues

Br J Cancer. 1999 May;80(3-4):364-70. doi: 10.1038/sj.bjc.6690364.


CPT-11 is a prodrug activated by carboxylesterases to the active metabolite SN-38 which is a potent inhibitor of topoisomerase I. CPT-11 is of clinical interest in the treatment of colorectal cancer. We evaluated the activities of CPT-11 converting carboxylesterase (CPT-CE) and topoisomerase I (topo I) in 53 colorectal tumours, in eight liver metastases and in normal tissue adjacent to the tumours. Both CPT-CE and topo I activities were widely variable in the malignant and the normal tissue of patients with colorectal carcinomas. CPT-CE was only two to threefold lower in primary tumours compared to normal liver, suggesting that a local conversion to SN-38 might occur in tumour cells. CPT-CE was similar in liver and in normal colon tissues. Levels of topo I in tumour ranged from 580 to 84 900 U mg protein(-1) and was above 40 000 U mg protein(-1) in 11 of 53 patients. Similarly, a very high ratio (> 5) between tumour and normal tissues were observed in 12 of 53 patients. An inverse correlation was observed between the topo I activity and the clinical stage of disease. Clinical studies are in progress in our institution to explore a possible relationship between CPT-CE and topo I activities in tumour cells and the response to CPT-11-based chemotherapy in patients with colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Carboxylic Ester Hydrolases / metabolism*
  • Colon / drug effects
  • Colon / enzymology*
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • DNA Topoisomerases, Type I / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Irinotecan
  • Liver / drug effects
  • Liver / enzymology*
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Rectal Neoplasms / enzymology*
  • Rectal Neoplasms / pathology
  • Topoisomerase I Inhibitors


  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • Irinotecan
  • CPT-11 converting enzyme
  • Carboxylic Ester Hydrolases
  • DNA Topoisomerases, Type I
  • Camptothecin