Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells

被引:54
作者
Vella, Serena [1 ]
Conti, Matteo [2 ]
Tasso, Roberta [1 ]
Cancedda, Ranieri [1 ,3 ]
Pagano, Aldo [1 ,3 ]
机构
[1] Univ Genoa, Oncol Biol & Genet Dept DOBiG, Genoa, Italy
[2] Osped S Maria delle Croci, Lab Clin Pharmacol & Toxicol, I-48100 Ravenna, Italy
[3] Natl Inst Canc Res IST Genoa, I-16132 Genoa, Italy
关键词
dichloroacetate; neuroblastoma; mitochondria; IN-VITRO; CANCER; APOPTOSIS; PHARMACOLOGY; METABOLISM; TOXICOLOGY; DCA;
D O I
10.1002/ijc.26173
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The small, water soluble molecule Dichloroacetate (DCA) is recently arousing lively interests in the field of cancer therapy for it has been shown to be able to inhibit the growth of human tumors acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells. Neuroblastoma was one of the tumor types on which DCA was considered ineffective as it is composed of cells with few recognized mitochondrial anomalies. Neuroblastoma, however, is composed of different cell types in terms of metabolism, phenotype and malignant potential. Despite the above prediction, in this work, we show that (i) DCA exhibits an unexpected anticancer effect on NB tumor cells and (ii) this effect is selectively directed to very malignant NB cells, whereas the more differentiated/less malignant NB cells are refractory to DCA treatment. This result supports the need of a detailed investigation of DCA anticancer properties against this tumor type with the final aim of its possible use as therapeutic agent.
引用
收藏
页码:1484 / 1493
页数:10
相关论文
共 29 条
[1]   E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation [J].
Almeida, Angeles ;
Bolanos, Juan P. ;
Moncada, Salvador .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (02) :738-741
[2]   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
[3]   Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation [J].
Cao, Wengang ;
Yacoub, Saif ;
Shiverick, Kathleen T. ;
Namiki, Kazunori ;
Sakai, Yoshihisa ;
Porvasnik, Stacy ;
Urbanek, Cydney ;
Rosser, Charles J. .
PROSTATE, 2008, 68 (11) :1223-1231
[4]   An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells [J].
Castelnuovo, Manuele ;
Massone, Sara ;
Tasso, Roberta ;
Fiorino, Gloria ;
Gatti, Monica ;
Robello, Mauro ;
Gatta, Elena ;
Berger, Audrey ;
Strub, Katharina ;
Florio, Tullio ;
Dieci, Giorgio ;
Cancedda, Ranieri ;
Pagano, Aldo .
FASEB JOURNAL, 2010, 24 (10) :4033-4046
[5]  
CHEN LB, 1988, ANNU REV CELL BIOL, V4, P155, DOI 10.1146/annurev.cellbio.4.1.155
[6]   H2O2-mediated Cytotoxicity of Pharmacologic Ascorbate Concentrations to Neuroblastoma Cells: Potential Role of Lactate and Ferritin [J].
Deubzer, Beate ;
Mayer, Florian ;
Kuci, Zyrafete ;
Niewisch, Marena ;
Merkel, Gisela ;
Handgretinger, Rupert ;
Bruchelt, Gernot .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2010, 25 (06) :767-774
[7]  
George RE, 2001, MED PEDIATR ONCOL, V36, P169, DOI 10.1002/1096-911X(20010101)36:1<169::AID-MPO1041>3.0.CO
[8]  
2-U
[9]   Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs [J].
Heshe, Dirk ;
Hoogestraat, Stephanie ;
Brauckmann, Christine ;
Karst, Uwe ;
Boos, Joachim ;
Lanvers-Kaminsky, Claudia .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2011, 67 (03) :647-655
[10]   Dichloroacetate causes toxic neuropathy in MELAS - A randomized, controlled clinical trial [J].
Kaufmann, P ;
Engelstad, K ;
Wei, Y ;
Jhung, S ;
Sano, MC ;
Shungu, DC ;
Millar, WS ;
Hong, X ;
Gooch, CL ;
Mao, X ;
Pascual, JM ;
Hirano, M ;
Stacpoole, PW ;
DiMauro, S ;
De Vivo, DC .
NEUROLOGY, 2006, 66 (03) :324-330