Novel function of N,N-bis(2-chloroethyl)docos-13-enamide for reversal of multidrug resistance in tongue cancer

作者：Qin, Qing; Ma, Peng-Fei; Kuang, Xiao-Cong; Gao, Ming-Xing; Mo, De-Huan; Xia, Shuang; Jin, Ning; Xia, Jun-Jie; Qi, Zhong-Quan^*; Lin, Cui-Wu

来源：European Journal of Pharmacology, 2013, 721(1-3): 208-214.

DOI：10.1016/j.ejphar.2013.09.033

• Compound J
• Multidrug resistance
• TCA8113/ADM
• P-glycoprotein
• GST
• GSH

Multidrug resistance (MDR) is a key element in the failure of chemotherapies, and development of agents to overcome MDR is crucial to improving cancer treatments. The overexpression of glutathione-S-transferases (GSTs) is one of the major mechanisms of MDR. Because some agents used in traditional Chinese medicine have strong antitumor effects coupled with low toxicity; we investigated the ability of N,N-bis(2-chloroethyl)docos-13-enamide (compound J), the synthesized analog of a highly unsaturated fatty acid from Isatis tinctoria L. to reverse the MDR induced by adriamycin (ADM) in TCA8113/ADM cells. We found that compound J significantly increased the cytotoxicity of ADM in TCA8113/ADM cells, with a reversal fold of 2.461. Analysis of the mechanisms through which compound J reversed MDR indicated that compound J significantly decreased the activity of GSTs and enhanced the depletion of GSH in TCA8113/ADM cells, but did not affect the P-glycoprotein (P-gp) efflux. Taken together, our data suggested that compound J was an excellent candidate for reversing MDR in cancer therapy.

• 出版日期2013-12-5
• 单位厦门大学; 广西医科大学; 广西大学