ArticleBMC cancer2021
Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Hypoxia-inducible factor 1α inhibitor reduces hippocampal neuronal ferroptosis.Neural regeneration research · 2026Article
- Revolutionizing Breast Cancer Treatment: Harnessing Ehrlich Ascites Carcinoma Model, Cancer Metabolism, and Nanotechnology-Enhanced Chemotherapy for Improved Patient Outcomes.Cell biochemistry and biophysics · 2026Review
- Luteolin Enhances Anticancer Effects of PX-478 during Hypoxic Response in Metastatic Breast Cancer Cells.Anti-cancer agents in medicinal chemistry · 2026Article
- Dichloroacetate enhances Chemo-sensitivity in wild-type P53 breast cancer cells by modulating ABCG2 and NKG2DL.Scientific reports · 2025Article
- Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer.Medical sciences (Basel, Switzerland) · 2025Review
- Curcumin-Dichloroacetate Hybrid Molecule as an Antitumor Oral Drug against Multidrug-Resistant Advanced Bladder Cancers.Cancers · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting mitochondrial bioenergetics by combination treatment with imatinib and dichloroacetate in human erythroleukemic K‑562 and colorectal HCT‑116 cancer cells.International journal of oncology · 2024Article
- Targeting Glucose Metabolism in Cancer Cells as an Approach to Overcoming Drug Resistance.Pharmaceutics · 2023Review
- AKT supports the metabolic fitness of multiple myeloma cells by restricting FOXO activity.Blood advances · 2023Article
- Glycolytic Inhibitors Potentiated the Activity of Paclitaxel and Their Nanoencapsulation Increased Their Delivery in a Lung Cancer Model.Pharmaceutics · 2022Article
- Design, Synthesis, and Molecular Docking Studies of Curcumin Hybrid Conjugates as Potential Therapeutics for Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesotheliomaFrontiers in pharmacology · 2022Article
- Metabolic Reprogramming Induces Macrophage Polarization in the Tumor Microenvironment.Frontiers in immunology · 2022Review
- DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia-Reperfusion by Regulating Glycolysis through PDK2-PDH-Nrf2 Axis.Oxidative medicine and cellular longevity · 2021Article
- Hypoxia and the Tumor Microenvironment.Technology in cancer research & treatmentReview
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOne key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Furthermore, the likelihood of drug resistance is reduced. Distinct alterations in tumor metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Recently, we found evidence for synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, and the HIF-1α inhibitor PX-478. In this study, we aimed to analyse this synergism in cell lines of different cancer types and to identify the underlying biochemical mechanisms.
methodsThe dose-dependent antiproliferative effects of the single drugs and their combination were assessed using SRB assays. FACS, Western blot and HPLC analyses were performed to investigate changes in reactive oxygen species levels, apoptosis and the cell cycle. Additionally, real-time metabolic analyses (Seahorse) were performed with DCA-treated MCF-7 cells.
resultsThe combination of DCA and PX-478 produced synergistic effects in all eight cancer cell lines tested, including colorectal, lung, breast, cervical, liver and brain cancer. Reactive oxygen species generation and apoptosis played important roles in this synergism. Furthermore, cell proliferation was inhibited by the combination treatment.
conclusionsHere, we found that these tumor metabolism-targeting compounds exhibited a potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.
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