Dichloroacetate affects proliferation but not apoptosis in canine mammary cell lines.

Abstract	Targeting mitochondrial energy metabolism is a novel approach in cancer research and can be traced back to the description of the Warburg effect. Dichloroacetate, a controversially discussed subject of many studies in cancer research, is a pyruvate dehydrogenase kinase inhibitor. Dichloroacetate causes metabolic changes in cancerous glycolysis towards oxidative phosphorylation via indirect activation of pyruvate dehydrogenase in mitochondria. Canine mammary cancer is frequently diagnosed but after therapy prognosis still remains poor. In this study, canine mammary carcinoma, adenoma and non-neoplastic mammary gland cell lines were treated using 10 mM Dichloroacetate. The effect on cell number, lactate release and PDH expression and cell respiration was investigated. Further, the effect on apoptosis and several apoptotic proteins, proliferation, and microRNA expression was evaluated. Dichloroacetate was found to reduce cell proliferation without inducing apoptosis in all examined cell lines.
Authors	Tatjana P Harting, Mandy Stubbendorff, Susanne C Hammer, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte
Journal	PloS one (PLoS One) Vol. 12 Issue 6 Pg. e0178744 ( 2017) ISSN: 1932-6203 [Electronic] United States
PMID	28591165 (Publication Type: Journal Article)
Chemical References	Inhibitor of Apoptosis Proteins MicroRNAs Pyruvate Dehydrogenase Acetyl-Transferring Kinase Lactic Acid Dichloroacetic Acid Protein Serine-Threonine Kinases
Topics	Animals Apoptosis (drug effects) Cell Count Cell Line Cell Proliferation (drug effects) Cell Respiration (drug effects) Dichloroacetic Acid (pharmacology) Dogs Female Inhibitor of Apoptosis Proteins (metabolism) Lactic Acid (metabolism) Mammary Glands, Animal (cytology) MicroRNAs (genetics, metabolism) Microscopy, Fluorescence Mitochondria (drug effects, metabolism) Phosphorylation (drug effects) Protein Serine-Threonine Kinases (metabolism) Pyruvate Dehydrogenase Acetyl-Transferring Kinase Time Factors

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