Details
| Original language | English |
|---|---|
| Pages (from-to) | 2341-2350 |
| Number of pages | 10 |
| Journal | International journal of oncology |
| Volume | 49 |
| Issue number | 6 |
| Early online date | 5 Oct 2016 |
| Publication status | Published - Dec 2016 |
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.
Keywords
- Adenocarcinoma/pathology, Animals, Apoptosis/drug effects, Carcinoma, Transitional Cell/pathology, Cell Line, Tumor, Cell Proliferation/drug effects, Cell Survival/drug effects, Dichloroacetic Acid/pharmacology, Dogs, Glycolysis/drug effects, Ketone Oxidoreductases/metabolism, Male, MicroRNAs/genetics, Mitochondria/metabolism, Oxidative Phosphorylation/drug effects, Prostate/metabolism, Prostatic Neoplasms/pathology, Protein Serine-Threonine Kinases/antagonists & inhibitors, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Dichloroacetate, Canine transitional cell carcinoma, Canine prostate adenocarcinoma, Warburg effect
ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Biochemistry, Genetics and Molecular Biology(all)
- Cancer Research
Sustainable Development Goals
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In: International journal of oncology, Vol. 49, No. 6, 12.2016, p. 2341-2350.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - The effect of dichloroacetate in canine prostate adenocarcinomas and transitional cell carcinomas in vitro
AU - Harting, Tatjana
AU - Stubbendorff, Mandy
AU - Willenbrock, Saskia
AU - Wagner, Siegfried
AU - Schadzek, Patrik
AU - Ngezahayo, Anaclet
AU - Murua Escobar, Hugo
AU - Nolte, Ingo
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Adenocarcinoma/pathology
KW - Animals
KW - Apoptosis/drug effects
KW - Carcinoma, Transitional Cell/pathology
KW - Cell Line, Tumor
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Dichloroacetic Acid/pharmacology
KW - Dogs
KW - Glycolysis/drug effects
KW - Ketone Oxidoreductases/metabolism
KW - Male
KW - MicroRNAs/genetics
KW - Mitochondria/metabolism
KW - Oxidative Phosphorylation/drug effects
KW - Prostate/metabolism
KW - Prostatic Neoplasms/pathology
KW - Protein Serine-Threonine Kinases/antagonists & inhibitors
KW - Pyruvate Dehydrogenase Acetyl-Transferring Kinase
KW - Dichloroacetate
KW - Canine transitional cell carcinoma
KW - Canine prostate adenocarcinoma
KW - Warburg effect
UR - http://www.scopus.com/inward/record.url?scp=84996527447&partnerID=8YFLogxK
U2 - 10.3892/ijo.2016.3720
DO - 10.3892/ijo.2016.3720
M3 - Article
C2 - 27748833
VL - 49
SP - 2341
EP - 2350
JO - International journal of oncology
JF - International journal of oncology
SN - 1019-6439
IS - 6
ER -