Tumor cell membrane as a potential target for methyl-beta-cyclodextrin.
The purpose of this work was to determine the role of methyl-beta-cyclodextrin (MEBCD) in combination with doxorubicin (DOX) on DOX intracellular accumulation and efflux, in comparison to verapamil in a sensitive parental and multidrug-resistant human cancer cell line (HL-60 S and HL-60 R). Moreover, cell membrane and nuclear modifications induced by MEBCD were investigated. At concentration of 10 mumol for 10(6) cells, MEBCD combined with doxorubicin (DOX), was able to significantly enhance the intracellular concentration of DOX in HL-60 S and HL-60 R cell lines during the period of exposure. In the resistant subline, MEBCD activity was higher than that of verapamil. Moreover, treatment of cells with MEBCD resulted in a modification in cell membrane integrity and cell morphology, but had no own activity in the distribution of the cells within cell cycle.
Grosse
P Y
PY
Department of Oncological Pharmacology, Val d'Aurelle Anticancer Center, Parc Euromedecine, Montpellier, France.
Bressolle
F
F
Vago
P
P
Simony-Lafontaine
J
J
Radal
M
M
Pinguet
F
F
D001692:Biological Transport / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D003505:Cyclodextrins / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D018922:HL-60 Cells; D006801:Humans; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D004317:Doxorubicin