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 up regulation 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.