Verapamil reverses the ultrastructural alterations in the plasma membrane induced by drug resistance

FEBS Letters

Soto, Florentina²  Garcia-Segura, Luis M.¹  Planells-Cases, Rosa²  Ferragut, Jose A.²  Gonzalez-Ros, Jose M.² 

[1] Cajal Institute, C.S.I.C., 28002 Madrid, Spain;Department of Neurochemistry and Institute of Neurosciences, University of Alicante, 03080 Alicante, Spain

关键词: Cellular drug resistance;    Verapamil;    Intramembrane particle;    Freeze-fracture;    DNM;    daunomycin;    VRP;    verapamil;    IMPs;    intramembrane particles;    P388/S;    DNM-sensitive P388 cells;    P388/20;    ∼ 20- fold DNM-resistant P388 cells;    P388/100;    ∼ 100-fold DNM-resistant P388 cells;    MDR;    cellular multi-drug resistance;    CHO;    Chinese hamster ovary cells;    P and E leaflets;    protoplasmic and exoplasmic leaflets of the plasma membrane;    respectively;   

DOI  :  10.1016/0014-5793(92)81515-N

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Two P388 cell sublines with different levels of resistance to daunomycin (DNM), P388/20 and P388/100 cells (∼ 20- and 100-fold resistance, respectively), undergo a significant (∼ 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 celIs. 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.

【 授权许可】

Unknown