Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | e0178744 |
| Fachzeitschrift | PLOS ONE |
| Jahrgang | 12 |
| Ausgabenummer | 6 |
| Publikationsstatus | Veröffentlicht - Juni 2017 |
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.
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in: PLOS ONE, Jahrgang 12, Nr. 6, e0178744, 06.2017.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Dichloroacetate affects proliferation but not apoptosis in canine mammary cell lines
AU - Harting, Tatjana P
AU - Stubbendorff, Mandy
AU - Hammer, Susanne C
AU - Schadzek, Patrik
AU - Ngezahayo, Anaclet
AU - Murua Escobar, Hugo
AU - Nolte, Ingo
N1 - Publisher Copyright: © 2017 Harting et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis/drug effects
KW - Cell Count
KW - Cell Line
KW - Cell Proliferation/drug effects
KW - Cell Respiration/drug effects
KW - Dichloroacetic Acid/pharmacology
KW - Dogs
KW - Female
KW - Inhibitor of Apoptosis Proteins/metabolism
KW - Lactic Acid/metabolism
KW - Mammary Glands, Animal/cytology
KW - MicroRNAs/genetics
KW - Microscopy, Fluorescence
KW - Mitochondria/drug effects
KW - Phosphorylation/drug effects
KW - Protein Serine-Threonine Kinases/metabolism
KW - Pyruvate Dehydrogenase Acetyl-Transferring Kinase
KW - Time Factors
UR - http://www.scopus.com/inward/record.url?scp=85020406485&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0178744
DO - 10.1371/journal.pone.0178744
M3 - Article
C2 - 28591165
VL - 12
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
M1 - e0178744
ER -