Sensitization of metformin-cytotoxicity by dichloroacetate via reprogramming glucose metabolism in cancer cells

被引：53

作者：

Choi, Yong Won ^{[1
]}

Lim, In Kyoung ^{[1
]}

机构：

[1] Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Cell Transformat & Restorat Project BK21, Suwon 443721, South Korea

来源：

CANCER LETTERS | 2014年 / 346卷 / 02期

关键词：

Metformin; Dichloroacetate (DCA); Oxidative stress; Glucose deprivation; Glutathione contents; RESPIRATORY-CHAIN; TUMOR-CELLS; COMPLEX-I; GROWTH; ACTIVATION; INHIBITION; AMPK; 2-DEOXYGLUCOSE; APOPTOSIS; DRUG;

D O I：

10.1016/j.canlet.2014.01.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To investigate sensitization of metformin-cytotoxicity, cancer cells were treated with dichloroacetate COCA), an inhibitor of pyruvate dehydrogenase kinase (PDK). Metformin-cytotoxicity was mainly dependent on glucose availability and reducing power generated by pentose phosphate pathway, whereas DCA cotreatment enhanced metformin-cytotoxicity via reprogramming glucose metabolism by inhibiting PDK and increasing mitochondrial respiration. DCA cotreatment elicited cell death rather than cell survival despite high glucose and high GSH condition. In conclusion, DCA sensitized metformin-cytotoxicity by reprogramming glucose metabolism in part from aerobic glycolysis to mitochondrial oxidation, evidenced by measurements of glucose consumption, lactate release, and the ratio of oxygen consumption rate/extracellular acidification rate. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：300 / 308

页数：9

共 36 条

[1] Mitochondrial O2-• and H2O2 mediate glucose deprivation-induced cytotoxicity and oxidative stress in human cancer cells [J].

Ahmad, IM ;

Aykin-Burns, N ;

Sim, JE ;

Walsh, SA ;

Higashikubo, R ;

Buettner, GR ;

Venkataraman, S ;

Mackey, MA ;

Flanagan, SW ;

Oberley, LW ;

Spitz, DR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (06) :4254-4263

[2] Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug? [J].

Ben Sahra, Issam ;

Le Marchand-Brustel, Yannick ;

Tanti, Jean-Francois ;

Bost, Frederic .

MOLECULAR CANCER THERAPEUTICS, 2010, 9 (05) :1092-1099

[3] Targeting Cancer Cell Metabolism: The Combination of Metformin and 2-Deoxyglucose Induces p53-Dependent Apoptosis in Prostate Cancer Cells [J].

Ben Sahra, Issam ;

Laurent, Kathiane ;

Giuliano, Sandy ;

Larbret, Frederic ;

Ponzio, Gilles ;

Gounon, Pierre ;

Le Marchand-Brustel, Yannick ;

Giorgetti-Peraldi, Sophie ;

Cormont, Mireille ;

Bertolotto, Corine ;

Deckert, Marcel ;

Auberger, Patrick ;

Tanti, Jean-Francois ;

Bost, Frederic .

CANCER RESEARCH, 2010, 70 (06) :2465-2475

[4] A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth [J].

Bonnet, Sebastien ;

Archer, Stephen L. ;

Allalunis-Turner, Joan ;

Haromy, Alois ;

Beaulieu, Christian ;

Thompson, Richard ;

Lee, Christopher T. ;

Lopaschuk, Gary D. ;

Puttagunta, Lakshmi ;

Bonnet, Sandra ;

Harry, Gwyneth ;

Hashimoto, Kyoko ;

Porter, Christopher J. ;

Andrade, Miguel A. ;

Thebaud, Bernard ;

Michelakis, Evangelos D. .

CANCER CELL, 2007, 11 (01) :37-51

[5] Cancer Cell Metabolism: One Hallmark, Many Faces [J].

Cantor, Jason R. ;

Sabatini, David M. .

CANCER DISCOVERY, 2012, 2 (10) :881-898

[6] Dual Inhibition of Tumor Energy Pathway by 2-Deoxyglucose and Metformin Is Effective against a Broad Spectrum of Preclinical Cancer Models [J].

Cheong, Jae-Ho ;

Park, Eun Sung ;

Liang, Jiyong ;

Dennison, Jennifer B. ;

Tsavachidou, Dimitra ;

Catherine Nguyen-Charles ;

Cheng, Kwai Wa ;

Hall, Hassan ;

Zhang, Dong ;

Lu, Yiling ;

Ravoori, Murali ;

Kundra, Vikas ;

Ajani, Jaffer ;

Lee, Ju-Seog ;

Hong, Waun Ki ;

Mills, Gordon B. .

MOLECULAR CANCER THERAPEUTICS, 2011, 10 (12) :2350-2362

[7] GLUTATHIONE DEPLETION, RADIOSENSITIZATION, AND MISONIDAZOLE POTENTIATION IN HYPOXIC CHINESE-HAMSTER OVARY CELLS BY BUTHIONINE SULFOXIMINE [J].

CLARK, EP ;

EPP, ER ;

BIAGLOW, JE ;

MORSEGAUDIO, M ;

ZACHGO, E .

RADIATION RESEARCH, 1984, 98 (02) :370-380

[8] Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I [J].

El-Mir, MY ;

Nogueira, V ;

Fontaine, E ;

Avéret, N ;

Rigoulet, M ;

Leverve, X .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (01) :223-228

[9] Warburg Effect and Redox Balance [J].

Hamanaka, Robert B. ;

Chandel, Navdeep S. .

SCIENCE, 2011, 334 (6060) :1219-1220

[10] CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth [J].

Ishimoto, Takatsugu ;

Nagano, Osamu ;

Yae, Toshifumi ;

Tamada, Mayumi ;

Motohara, Takeshi ;

Oshima, Hiroko ;

Oshima, Masanobu ;

Ikeda, Tatsuya ;

Asaba, Rika ;

Yagi, Hideki ;

Masuko, Takashi ;

Shimizu, Takatsune ;

Ishikawa, Tomoki ;

Kai, Kazuharu ;

Takahashi, Eri ;

Imamura, Yu ;

Baba, Yoshifumi ;

Ohmura, Mitsuyo ;

Suematsu, Makoto ;

Baba, Hideo ;

Saya, Hideyuki .

CANCER CELL, 2011, 19 (03) :387-400

← 1 2 3 4 →