Verapamil reverses the ultrastructural alterations in the plasma membrane induced by drug resistance.
Two P388 cell sublines with different levels of resistance to daunomycin (DNM), P388/20 and P388/100 cells (approximately 20- and 100-fold resistance, respectively), undergo a significant (approximately 2-fold) increase in the number of intramembrane particles (IMPs) present at their plasma membrane, as compared to that exhibited by the parental, drug-sensitive P388 (P388/S) cell line. Regardless of the level of resistance, incubation of drug-resistant cells with verapamil, a well known reverting agent of anthracycline resistance, restores the morphology of the plasma membrane in these cells, yielding a pattern in which the number and size distribution of IMPs at both leaflets of the bilayer, become undistinguishable from those displayed by drug-sensitive cells. Furthermore, verapamil did not affect the ultrastructural organization of the plasma membrane of drug-sensitive cells. It is possible that the alterations in the structural organization of the plasma membrane of the antineoplastic-resistant tumor cells, might represent a reliable 'marker' for early diagnosis of drug resistance.
García-Segura
L M
LM
Cajal Institute, C.S.I.C., Madrid, Spain.
Soto
F
F
Planells-Cases
R
R
Gonzalez-Ros
J M
JM
Ferragut
J A
JA
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D003630:Daunorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005614:Freeze Fracturing; D007941:Leukemia P388; D008562:Membrane Glycoproteins; D051379:Mice; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D008562:Membrane Glycoproteins; D014700:Verapamil; D003630:Daunorubicin