ArticleBiochimica et biophysica acta2016
GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Dual-action mitochondria-targeted prodrugs that both deplete mitochondrial glutathione and deliver a toxic payload to the matrix.European journal of medicinal chemistry · 2026Article
- Subtype-specific alternative splicing events in breast cancer identified by large-scale data analysis.Scientific reports · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Human mitochondrial glutathione transferases: Kinetic parameters and accommodation of a mitochondria-targeting group in substrates.Bioorganic & medicinal chemistry · 2024Article
- Chemical Proteomics with Novel Fully Functionalized Fragments and Stringent Target Prioritization Identifies the Glutathione-Dependent Isomerase GSTZ1 as a Lung Cancer Target.ACS chemical biology · 2023Article
- Dysregulated glucuronic acid metabolism exacerbates hepatocellular carcinoma progression and metastasis through the TGFβ signalling pathway.Clinical and translational medicine · 2022Article
- Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature.Frontiers in immunology · 2022Article
- GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells.FEBS open bio · 2020Article
- Unveiling prognostics biomarkers of tyrosine metabolism reprogramming in liver cancer by cross-platform gene expression analyses.PloS one · 2020Article
- Oncometabolite modification of Keap1 links GSTZ1 deficiency with cancer.Genes & diseases · 2019Article
- GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.The EMBO journal · 2019Article
- Age-associated changes in GSH S-transferase gene/proteins in livers of rats.Redox report : communications in free radical research · 2018Article
- Regulation of dichloroacetate biotransformation in rat liver and extrahepatic tissues by GSTZ1 expression and chloride concentration.Biochemical pharmacology · 2018Article
- Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases.Oncogenesis · 2018Review
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Dichloroacetate (DCA), commonly used to treat metabolic disorders, is under investigation as an anti-cancer therapy due to its ability to reverse the Warburg effect and induce apoptosis in tumor cells. While DCA's mechanism of action is well-studied, other factors that influence its potential as a cancer treatment have not been thoroughly investigated. Here we show that expression of glutathione transferase zeta 1 (GSTZ1), the enzyme responsible for conversion of DCA to its inactive metabolite, glyoxylate, is downregulated in liver cancer and upregulated in some breast cancers, leading to abnormal expression of the protein. The cellular concentration of chloride, an ion that influences the stability of GSTZ1 in the presence of DCA, was also found to be abnormal in tumors, with consistently higher concentrations in hepatocellular carcinoma than in surrounding non-tumor tissue. Finally, results from experiments employing two- and three-dimensional cultures of HepG2 cells, parental and transduced to express GSTZ1, demonstrate that high levels of GSTZ1 expression confers resistance to the effect of high concentrations of DCA on cell viability. These results may have important clinical implications in determining intratumoral metabolism of DCA and, consequently, appropriate oral dosing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.