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Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation
Authors Duan Y, Zhao X, Ren W, Wang X, Yu K, Li D, Zhang X , Zhang Q
Received 30 November 2012
Accepted for publication 4 February 2013
Published 14 March 2013 Volume 2013:6 Pages 189—198
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 5
Yu Duan,1 Xin Zhao,1 Wei Ren,1 Xin Wang,1 Ke-Fu Yu,1 Dan Li,1 Xuan Zhang,1 Qiang Zhang1,2
1Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China; 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China
Abstract: Dichloroacetate (DCA), a small molecule mitochondria-targeting agent, can penetrate the blood–brain barrier, showing potential therapeutic effects on brain tumors. Considering the effects of DCA on tumor cellular metabolism, penetrating across the blood–brain barrier, as well as having potential antitumor activity on brain tumors, the purpose of this study is to investigate the antitumor activity of DCA on C6 glioma cells in vitro and in vivo. DCA inhibited C6 glioma cell proliferation, induced C6 cell apoptosis, and arrested C6 cells in S phase. DCA can inhibit the expression of heat shock proteins 70 (Hsp70) in a dose-dependent and time-dependent manner (P < 0.01). Our in vivo antitumor effect results indicated that DCA markedly inhibited the growth of C6 glioma tumors in both C6 brain tumor-bearing rats and C6 tumor-bearing nude mice (P <0.01). DCA significantly induced the ROS production and decreased the mitochondrial membrane potential in tumor tissues. Our in vivo antitumor effect results also indicated that DCA has potential antiangiogenic effects. In conclusion, DCA may be a viable therapeutic agent in the treatment of gliomas.
Keywords: dichloroacetate, DCA, C6 glioma, antitumor efficacy, in vitro, in vivo
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