Dichloroacetate affects proliferation but not apoptosis in canine mammary cell lines

authored by

Tatjana P Harting, Mandy Stubbendorff, Susanne C Hammer, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte

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.

Organisation(s)

Institute of Cell Biology and Biophysics

External Organisation(s)

University of Veterinary Medicine of Hannover, Foundation
Evotec ID (Marcy l'Etoile)

Type

Article

Journal

PLOS ONE

Volume

12

ISSN

1932-6203

Publication date

06.2017

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

General

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1371/journal.pone.0178744 (Access: Open)