American Journal of Cancer Prevention
ISSN (Print): 2328-7314 ISSN (Online): 2328-7322 Website: Editor-in-chief: Nabil Abdel-Hamid
Open Access
Journal Browser
American Journal of Cancer Prevention. 2018, 6(1), 5-8
DOI: 10.12691/ajcp-6-1-2
Open AccessArticle

Dichloroacetate is Promising for Treating Hematological Malignancy through Inhibiting Ketone Bodies Oxidation: towards Better Understanding of Its Anticancer Mechanisms

Mongi Ayat1,

1Division of Hematology, Department of Clinical Biochemistry and Molecular Medicine, Taibah College of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

Pub. Date: March 06, 2018

Cite this paper:
Mongi Ayat. Dichloroacetate is Promising for Treating Hematological Malignancy through Inhibiting Ketone Bodies Oxidation: towards Better Understanding of Its Anticancer Mechanisms. American Journal of Cancer Prevention. 2018; 6(1):5-8. doi: 10.12691/ajcp-6-1-2


Dichloroacetate (DCA) is a promising anticancer drug that exerts potent anticancer effects in many clinical oncology studies. On biochemical and pharmacological bases, this article aims at gaining a better understanding of DCA anticancer effects. Ketone bodies oxidation (ketolysis) is an important source of energy to many cancer cells. Here, it is proved that DCA antagonizes acetoacetate and targets cancer cells' energetics through inhibiting ketolysis as novel evidence-based anticancer mechanisms. DCA was reported to inhibit oxidation of both ketone bodies (acetoacetate and β-hydroxybutyrate) in addition to palmitate. Acetoacetate diverted pyruvate metabolism from pyruvate dehydrogenase (PDH) to pyruvate carboxylation while DCA increased the oxidation of glucose through PDH. This suggests an antagonism between DCA and ketone bodies. Moreover, DCA was reported to inhibit β-hydroxybutyrate uptake by the extra-splanchnic tissues and decrease the clearance of ketone bodies. That may be explained by structural antagonism between DCA and ketone bodies leading to a competitive uptake at target tissues i.e. DCA may competitively antagonize ketone bodies. In a previous study, DCA infusion in starved rats caused a significant decrease in blood glucose, plasma insulin, blood lactate and pyruvate concentrations but significantly increased concentrations of ketone bodies (β-hydroxybutyrate and acetoacetate) (Blackshear et al., 1974). Based on that, DCA inhibits ketone bodies utilization for energy production. In conclusion, DCA enhances anticancer immunity, targets anaerobic cancer cell populations (via targeting Warburg effect) and targets aerobic cancer cell populations through targeting mitochondrial energy generating pathways e.g. ketolysis.

dichloroacetate cancer ketolysis Warburg effect

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  Dunbar EM, Coats BS, Shroads AL, Langaee T, Lew A, Forder JR, Shuster JJ, Wagner DA, Stacpoole PW. Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors. Invest New Drugs. 2014 Jun; 32(3): 452-64.
[2]  Strum SB, Adalsteinsson O, Black RR, Segal D, Peress NL, Waldenfels J. Case report: Sodium dichloroacetate (DCA) inhibition of the "Warburg Effect" in a human cancer patient: complete response in non-Hodgkin's lymphoma after disease progression with rituximab-CHOP. J Bioenerg Biomembr. 2013 Jun; 45(3):307-15.
[3]  Tong J, Xie G, He J, Li J, Pan F, Liang H. Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer. J Biomed Biotechnol. 2011; 2011: 740564.
[4]  El Sayed SM, Mohamed WG, Seddik MA, Ahmed AS, Mahmoud AG, Amer WH, Helmy Nabo MM, Hamed AR, Ahmed NS, Abd-Allah AA. Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study. Chin J Cancer. 2014 Jul; 33(7): 356-64.
[5]  Denise R. Ferrier Lippincott's illustrated reviews Biochemistry 6th edition. Wolters Klower. Lippincott Williams and Wilkins. 2014. Page 332
[6]  Zhang S, Xie C. The role of OXCT1 in the pathogenesis of cancer as a rate-limiting enzyme of ketone body metabolism. Life Sci. 2017 Aug 15; 183: 110-115.
[7]  Orii KE, Fukao T, Song XQ, Mitchell GA, Kondo N. Liver-specific silencing of the human gene encoding succinyl-CoA: 3-ketoacid CoA transferase. Tohoku J Exp Med. 2008 Jul; 215(3): 227-36.
[8]  Huang, Li T, Wang L, Zhang L, Yan R, Li K, Xing S, Wu G, Hu L, Jia W, Lin SC, Dang CV, Song L, Gao P, Zhang H. Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress. Cell Res. 2016 Oct; 26(10): 1112-1130.
[9]  Galluzzi L, Kroemer G. Aberrant ketolysis fuels hepatocellular cancer progression. Cell Res. 2016 Oct; 26(10):1077-1078.
[10]  Ferreira LM. Cancer metabolism: the Warburg effect today. Exp Mol Pathol. 2010 Dec; 89(3): 372-80.
[11]  McAllister A, Allison SP, Randle PJ. Effects of dichloroacetate on the metabolism of glucose, pyruvate, acetate, 3-hydroxybutyrate and palmitate in rat diaphragm and heart muscle in vitro and on extraction of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo. Biochem J. 1973 Aug; 134(4): 1067-81.
[12]  Blackshear PJ, Holloway PA, Alberti KG. The metabolic effects of sodium dichloroacetate in the starved rat. Biochem J. 1974 Aug; 142(2): 279-86.
[13]  Blackshear PJ, Holloway PA, Alberti KG. Metabolic interactions of dichloroacetate and insulin in experimental diabetic ketoacidosis. Biochem J. 1975 Feb; 146(2): 447-56.
[14]  Stacpoole PW, Greene YJ. Dichloroacetate. Diabetes Care. 1992 Jun; 15(6): 785-91.
[15]  Stacpoole PW, Henderson GN, Yan Z, James MO. Clinical pharmacology and toxicology of dichloroacetate. Environ Health Perspect. 1998 Aug; 106 Suppl 4: 989-94.