title: HDAC inhibitor-induced drug resistance involving ATP-binding cassette transporters (Review).
abstract: Histone deacetylase (HDAC) inhibitors are becoming a novel and promising class of antineoplastic agents that have been used for cancer therapy in the clinic. Two HDAC inhibitors, vorinostat and romidepsin, have been approved by the Food and Drug Administration to treat T-cell lymphoma. Nevertheless, similar to common anticancer drugs, HDAC inhibitors have been found to induce multidrug resistance (MDR), which is an obstacle for the success of chemotherapy. The most common cause of MDR is considered to be the increased expression of adenosine triphosphate binding cassette (ABC) transporters. Numerous studies have identified that the upregulation of ABC transporters is often observed following treatment with HDAC inhibitors, particularly the increased expression of P-glycoprotein, which leads to drug efflux, reduces intracellular drug concentration and induces MDR. The present review summarizes the key ABC transporters involved in MDR following various HDAC inhibitor treatments in a range of cancer cell lines and also explored the potential mechanisms that result in MDR, including the effect of nuclear receptors, which are the upstream regulatory factors of ABC transporters.
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Ni
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993-0002, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Pan
keywords: P-glycoprotein; breast cancer resistance protein; cancer treatment; histone deacetylase inhibitors; multidrug resistance; multidrug resistance protein 1/2; nuclear receptor