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Susceptibility of multidrug resistance tumor cells to apoptosis induction by histone deacetylase inhibitors
Author(s) -
CastroGalache Maria D.,
Ferragut Jose A.,
Barbera Victor M.,
MartínOrozco Elena,
GonzalezRos Jose M.,
GarciaMorales Pilar,
Saceda Miguel
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10998
Subject(s) - trichostatin a , histone deacetylase , vorinostat , histone deacetylase 2 , histone deacetylase inhibitor , histone deacetylase 5 , cancer research , biology , hdac11 , multiple drug resistance , apoptosis , histone , drug resistance , biochemistry , genetics , gene
Abstract The main goal of our study has been to analyze the efficiency of new anticancer drugs, specifically histone deacetylase inhibitors, in tumor cells bearing a multidrug resistance phenotype. We report that the histone deacetylase inhibitors, Trichostatin A and Suberoylanilide Hydroxamic Acid (SAHA), dramatically reduce cell viability and promote apoptosis in different drug‐resistant cells, affecting in a much lesser extent to their parental drug‐sensitive counterparts. The differential effects induced by Trichostatin A and SAHA between drug‐sensitive and drug‐resistant cells are reflected on the main characteristics of the resistant phenotype. Thus, reverse transcription‐PCR and Western immunoblots confirm that both histone deacetylase inhibitors promote endogenous down‐regulation of P‐glycoprotein, which is overexpressed in the drug‐resistant cells. Transfection of drug‐sensitive cells with the P‐glycoprotein cDNA ruled out the a priori possible association between apoptosis and down‐regulation of P‐glycoprotein induced by the histone deacetylase inhibitors. The results suggest a therapeutic potential of histone deacetylase inhibitors in the treatment of cancers with acquired resistance. © 2003 Wiley‐Liss, Inc.