Danks_1998_Cancer.Res_58_20

Reference

Title : Overexpression of a rabbit liver carboxylesterase sensitizes human tumor cells to CPT-11 - Danks_1998_Cancer.Res_58_20
Author(s) : Danks MK , Morton CL , Pawlik CA , Potter PM
Ref : Cancer Research , 58 :20 , 1998
Abstract :

CPT-11 [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin ] is a prodrug that is converted to the active metabolite SN-38 by carboxylesterases. In its active form, the drug inhibits topoisomerase I, causes DNA damage, and induces apoptosis. Data in this study show metabolism of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin) by a rabbit liver carboxylesterase in vitro and growth-inhibitory activity of the products of the reaction. Additionally, stable expression of the cDNA encoding this protein in Rh30 human rhabdomyosarcoma cells increased the sensitivity of the cells to CPT-11 8.1-fold. We propose that this prodrug/enzyme combination can be exploited therapeutically in a manner analogous to approaches currently under investigation with the combinations of ganciclovir/herpes simplex virus thymidine kinase and 5-fluorocytosine/cytosine deaminase.

PubMedSearch : Danks_1998_Cancer.Res_58_20
PubMedID: 9426050
Gene_locus related to this paper: rabit-1cxes

Related information

Inhibitor Irinotecan
Substrate Irinotecan    Irinotecan
Gene_locus Irinotecan    Irinotecan    rabit-1cxes

Citations formats

Danks MK, Morton CL, Pawlik CA, Potter PM (1998)
Overexpression of a rabbit liver carboxylesterase sensitizes human tumor cells to CPT-11
Cancer Research 58 :20

Danks MK, Morton CL, Pawlik CA, Potter PM (1998)
Cancer Research 58 :20