Dichloroacetate Affects Mitochondrial Function and Stemness-Associated Properties in Pancreatic Cancer Cell Lines
Related Experiment Video
Updated: Jan 24, 2026
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
Tiziana Tataranni1, Francesca Agriesti2, Consiglia Pacelli3
1Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture (Pz), Italy. tiziana.tataranni@crob.it.
Abstract:
Targeting metabolism represents a possible successful approach to treat cancer. Dichloroacetate (DCA) is a drug known to divert metabolism from anaerobic glycolysis to mitochondrial oxidative phosphorylation by stimulation of PDH. In this study, we investigated the response of two pancreatic cancer cell lines to DCA, in two-dimensional and three-dimension cell cultures, as well as in a mouse model. PANC-1 and BXPC-3 treated with DCA showed a marked decrease in cell proliferation and migration which did not correlate with enhanced apoptosis indicating a cytostatic rather than a cytotoxic effect. Despite PDH activation, DCA treatment resulted in reduced mitochondrial oxygen consumption without affecting glycolysis. Moreover, DCA caused enhancement of ROS production, mtDNA, and of the mitophagy-marker LC3B-II in both cell lines but reduced mitochondrial fusion markers only in BXPC-3. Notably, DCA downregulated the expression of the cancer stem cells markers CD24/CD44/EPCAM only in PANC-1 but inhibited spheroid formation/viability in both cell lines. In a xenograft pancreatic cancer mouse-model DCA treatment resulted in retarding cancer progression. Collectively, our results clearly indicate that the efficacy of DCA in inhibiting cancer growth mechanistically depends on the cell phenotype and on multiple off-target pathways. In this context, the novelty that DCA might affect the cancer stem cell compartment is therapeutically relevant.
Insights
Dichloroacetate (DCA) drug inhibits pancreatic cancer growth by affecting cell metabolism and stemness, showing cytostatic effects rather than cell death. DCA retards tumor progression in mouse models, highlighting its therapeutic potential.
Area of Science:
- Oncology
- Metabolic pathways
- Cancer research
Background:
- Targeting cancer metabolism is a promising therapeutic strategy.
- Dichloroacetate (DCA) modulates cellular metabolism by stimulating pyruvate dehydrogenase (PDH).
Purpose of the Study:
- To investigate the effects of DCA on pancreatic cancer cell lines (PANC-1, BXPC-3) in vitro and in vivo.
- To elucidate the mechanisms underlying DCA's anti-cancer activity, including its impact on metabolism and cancer stem cell markers.
Main Methods:
- Two-dimensional and three-dimensional cell cultures of pancreatic cancer cell lines.
- Treatment with Dichloroacetate (DCA).
- Assessment of cell proliferation, migration, apoptosis, mitochondrial respiration, ROS production, mitophagy, mitochondrial fusion, cancer stem cell markers, and spheroid formation.
- Evaluation in a xenograft pancreatic cancer mouse model.
Main Results:
- DCA decreased proliferation and migration in PANC-1 and BXPC-3 cells, indicating cytostatic effects.
- DCA reduced mitochondrial oxygen consumption and glycolysis, increased ROS production, and enhanced mitophagy markers.
- DCA affected cancer stem cell markers and spheroid formation differently across cell lines but inhibited overall spheroid viability.
- DCA treatment retarded tumor progression in a pancreatic cancer xenograft mouse model.
Conclusions:
- DCA exhibits anti-cancer effects in pancreatic cancer models through cytostatic mechanisms.
- DCA's efficacy is dependent on cell phenotype and involves multiple off-target pathways, including effects on cancer stem cells.
- DCA's impact on the cancer stem cell compartment presents a novel therapeutic avenue for pancreatic cancer treatment.
Related Concept Videos
01:25Properties of Electric Field Lines
For one, the electric field of a positive charge must originate from it. That is because its electric field points away from it. Moreover, since the magnitude of the field asymptotes to zero at infinity, the...
01:18Distinctive Features of Adult Stem Cells vs Cancer Stem Cells
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
01:33Adult Stem Cells
01:16Cell Lines
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
02:59Animal Mitochondrial Genetics