The effect of dichloroacetate in canine prostate adenocarcinomas and transitional cell carcinomas in vitro

authored by

Tatjana Harting, Mandy Stubbendorff, Saskia Willenbrock, Siegfried Wagner, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte

Abstract

The Warburg effect describes the ability of cancer cells to produce energy via aerobic glycolysis instead of oxidative phosphorylation of pyruvate. This deviation in mitochondrial metabolism inhibits apoptosis, allowing increased proliferation under conditions of reduced oxygen levels. Dichloroacetate (DCA) was successfully used in several human cancer cell lines to reactivate oxidative phosphorylation in mitochondria. The aim of this study was the characterization and response of canine cancer cell lines after DCA exposure. The effect of 10 mM DCA was characterized in vitro on a set of six canine prostate adenocarcinoma and transitional cell carcinoma (TCC) derived cell lines. Cell counts, lactate levels, apoptosis, expression of apoptotic proteins, survival factors and different miRNAs were analyzed. Additionally, metabolic activity, mitochondrial activity and proliferation were investigated. DCA significantly decreased cell number of all but one utilized cell lines and leads to a significant reduction of lactate release. Decreased survivin levels were found in all cell lines, two of which presented a significant reduction in metabolic activity. Increased miR-375 levels were measured in all TCC cell lines. Reactivation of pyruvate dehydrogenase and an elevated mitochondrial activity appear to induce the transition from aerobic glycolysis back to oxidative phosphorylation. Further, these results display that DCA treatment has a suppressant effect on proliferation of canine cancer cells.

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

International journal of oncology

Volume

49

Pages

2341-2350

No. of pages

10

ISSN

1019-6439

Publication date

12.2016

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Oncology, Cancer Research

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.3892/ijo.2016.3720 (Access: Closed)