Kim, Yong Kee Kim, Nam Hyun Hwang, Jee Won Song, Yong-Jin Park, Yeon-Suk Seo, Dong-Wan Lee, Hoi Young Choi, Wahn Soo Han, Jeung-Whan Kim, Su-Nam 2024-01-20T23:31:27Z 2024-01-20T23:31:27Z 2021-09-03 2008-04-18 0006-291X https://pubs.kist.re.kr/handle/201004/133547 Multidrug resistance (MDR), which is a significant impediment to the success of cancer chemotherapy, is attributable to the overexpression of membrane transport proteins, such as P-glycoprotein (P-gp), resulting in an increased drug efflux. In this study, we show that the histone deacetylase (HDAC) inhibitor apicidin leads to resistance of HeLa cells to paclitaxel through the induction of P-gp expression. Furthermore, apicidin dramatically increases the release of a fluorescent P-gp substrate, rhodamine 123, from cells. In parallel, apicidin resistance to the apoptotic potential of paclitaxel is associated with induction of P-gp expression in HeLa cells, as evidenced by specific inhibition of P-gp function using either the pharmacological inhibitor verapamil or RNA silencing. We also demonstrate the contribution of apicidin-induced functional P-gp expression to drug resistance using KB cells. Failure of P-gp induction by apicidin does not reverse paclitaxel-induced cytotoxicity in the cells. Although HDAC inhibitors are widely appreciated as a new class of antitumor agent, our findings clearly demonstrate that apicidin treatment may lead to P-gp-mediated resistance to other anti-tumor agents, suggesting a need for careful design of clinical applications using HDAC inhibitors. (C) 2008 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE PROMYELOCYTIC LEUKEMIA-CELLS NF-KAPPA-B MULTIDRUG-RESISTANCE MDR1 GENE DEPSIPEPTIDE FK228 MYELOID-LEUKEMIA SP1 SITES PHASE-I ACTIVATION EXPRESSION Histone deacetylase inhibitor apicidin-mediated drug resistance: Involvement of P-glycoprotein Article 10.1016/j.bbrc.2008.02.013 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.368, no.4, pp.959 - 964 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 368 4 959 964 scie scopus 000254106700021 2-s2.0-40049111860 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article PROMYELOCYTIC LEUKEMIA-CELLS NF-KAPPA-B MULTIDRUG-RESISTANCE MDR1 GENE DEPSIPEPTIDE FK228 MYELOID-LEUKEMIA SP1 SITES PHASE-I ACTIVATION EXPRESSION multidrug resistance P-glycoprotein HDAC inhibitor apicidin apoptosis