Susceptibility of multidrug resistance tumor cells to apoptosis induction by histone deacetylase inhibitors

✍ Scribed by Maria D. Castro-Galache; Jose A. Ferragut; Victor M. Barbera; Elena Martín-Orozco; Jose M. Gonzalez-Ros; Pilar Garcia-Morales; Miguel Saceda

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 391 KB
• Volume: 104
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.10998

✦ Synopsis

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.