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Verapamil reverses the ultrastructural alterations in the plasma membrane induced by drug resistance
Author(s) -
Garcia-Segura Luis M.,
Soto Florentina,
Planells-Cases Rosa,
Gonzalez-Ros Jose M.,
Ferragut Jose A.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81515-n
Subject(s) - verapamil , ultrastructure , pharmacology , drug , chemistry , membrane , medicine , biochemistry , calcium , anatomy
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.