Novel function of N,N-bis(2-chloroethyl)docos-13-enamide for reversal of multidrug resistance in tongue cancer.
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.
College of Chemistry and Chemical Engineering, Guangxi University, Nanning city, Guangxi province 530004, PR China; School of Pharmaceutical Sciences, Guangxi Medical University, Nanning city, Guangxi province, PR China. Electronic address: qqyx103@163.com.
Qing
Q
Qin
Peng-Fei
PF
Ma
Xiao-Cong
XC
Kuang
Ming-Xing
MX
Gao
De-Huan
DH
Mo
Shuang
S
Xia
Ning
N
Jin
Jun-Jie
JJ
Xia
Zhong-Quan
ZQ
Qi
Cui-Wu
CW
Lin
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004883:Erucic Acids / Q000737:chemistry* / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D014062:Tongue Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D004883:Erucic Acids; D005227:Fatty Acids; C000589514:N,N-bis(2-chloroethyl)docos-13-enamide; D004317:Doxorubicin; D005982:Glutathione Transferase; D005978:Glutathione
Compound J; GSH; GST; Multidrug resistance; P-glycoprotein; TCA8113/ADM