title: Superior anti-tumor efficacy of diisopropylamine dichloroacetate compared with dichloroacetate in a subcutaneous transplantation breast tumor model.
abstract: Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has anti-tumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, were used in in vitro and in vivo experiments to evaluate the anti-tumor efficacy of DADA and DCA. The half maximal inhibitory concentration (IC50) of DADA (7.1 ± 1.1 mmol/L) against MDA-MB-231 cells was significantly lower than that of DCA (15.6 ± 2.0 mmol/L); 100 mg/kg (0.0004 mol/kg) DADA was better than 100 mg/kg (0.0008 mol/kg) DCA at suppressing the growth of subcutaneous transplantation breast tumor at the same dose after 24 days intervention. Histological examination showed that both DCA and DADA interventions led to necrosis, inflammation, and fibrosis of tumor tissue in a mouse subcutaneous transplantation breast tumor model. DADA treatment inhibited Ki67 expression in tumor tissue. In vitro experiments showed that DADA could inhibit lactic acid production and glucose uptake in MDA-MB-231 cells at 10 mmol/L and these effects were stronger than DCA. DADA administration also induced complete autophagy during early treatment stages and incomplete autophagy and cell death at later treatment stages. In conclusion, DADA showed better anti-tumor efficacy than DCA in a breast cancer model.
authors: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. of China.
authors: Lei
authors: L
authors: Su
authors: Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008, P.R. of China.
authors: Hailin
authors: H
authors: Zhang
authors: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. of China.
authors: Chen
authors: C
authors: Yan
authors: Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008, P.R. of China.
authors: Aiping
authors: A
authors: Chen
authors: Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008, P.R. of China.
authors: Gang
authors: G
authors: Meng
authors: Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008, P.R. of China.
authors: Jiwu
authors: J
authors: Wei
authors: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. of China.
authors: Decai
authors: D
authors: Yu
authors: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. of China.
authors: Yitao
authors: Y
authors: Ding
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000644:Quaternary Ammonium Compounds; C001002:diisopropylamine dichloroacetate; D003999:Dichloroacetic Acid
keywords: MDA-MB-231 cell line; dichloroacetate; diisopropylamine dichloroacetate; subcutaneous transplantation breast tumor model