RT Journal Article
SR Electronic
T1 Reversal of the Multidrug Resistance Phenotype with Cremophor EL, a Common Vehicle for Water-insoluble Vitamins and Drugs
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 4199
OP 4203
VO 50
IS 14
A1 Woodcock, David M.
A1 Jefferson, Sara
A1 Linsenmeyer, Martha E.
A1 Crowther, Penelope J.
A1 Chojnowski, Grace M.
A1 Williams, Brenda
A1 Bertoncello, Ivan
YR 1990
UL http://cancerres.aacrjournals.org/content/50/14/4199.abstract
AB A polyethoxylated castor oil, Cremophor EL, which is used as a vehicle for p.o. and i.v. administration of water-insoluble compounds in humans, can reverse the multidrug resistance (MDR) phenotype at doses which are likely to be readily achievable clinically. Using flow cytofluorometric analysis of daunorubicin (DNR) uptake as a measure of the expression of the MDR phenotype, Cremophor EL (1:103) in the growth medium increased intracellular DNR in an MDR cell line, R100 cells, to levels similar to that observed in the drug-sensitive parental cells, CCRFCEM. A similar Cremophor EL-induced increase in DNR uptake was also observed in an unrelated MDR cell line derived from K562 cells. Cremophor EL (≤3:104) did not inhibit the growth of CCRF-CEM cells or its vinblastine-resistant derivative, R100 cells, but would significantly increase the sensitivity of R100 cells to both vinblastine and DNR. Also Cremophor EL did not increase the sensitivity of normal bone marrow progenitor cells cultured in vitro to high concentrations of vinblastine. Cremophor EL may prove to be a relatively pharmacologically inactive addition to chemotherapeutic protocols which may be able to reverse the MDR phenotype in tumors and also help to prevent the selection of MDR cell variants from within a tumor cell population during chemotherapy. ©1990 American Association for Cancer Research.