ArticleJournal of bioenergetics and biomembranes2012
Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition.
Article in Journal of bioenergetics and biomembranes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- METTL3 knockout accelerates hepatocarcinogenesis via inhibiting endoplasmic reticulum stress response.FEBS open bio · 2025Article
- The Role of Reprogrammed Glucose Metabolism in Cancer.Metabolites · 2023Review
- Targeted Inhibition of P4HB Promotes Cell Sensitivity to Gemcitabine in Urothelial Carcinoma of the Bladder.OncoTargets and therapy · 2020Article
- Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma.International journal of molecular sciences · 2019Article
- 3‑Bromopyruvate sensitizes human breast cancer cells to TRAIL‑induced apoptosis via the phosphorylated AMPK‑mediated upregulation of DR5.Oncology reports · 2018Article
- Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2018Article
- Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway.Oncogene · 2017Article
- Review
- P4HB promotes HCC tumorigenesis through downregulation of GRP78 and subsequent upregulation of epithelial-to-mesenchymal transition.Oncotarget · 2017Article
- Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate.Frontiers in oncology · 2017Review
- A substrate-driven allosteric switch that enhances PDI catalytic activity.Nature communications · 2016Article
- The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside.Journal of bioenergetics and biomembranes · 2016Review
- Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection.BMC gastroenterology · 2016Article
- Bacitracin Inhibits the Migration of U87-MG Glioma Cells via Interferences of the Integrin Outside-in Signaling Pathway.Journal of Korean Neurosurgical Society · 2016Article
- The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression.Bioscience reports · 2016Article
- Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model.Journal of cancer research and clinical oncology · 2015Article
- Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication.World journal of biological chemistry · 2015Review
- Maternal nicotine exposure leads to impaired disulfide bond formation and augmented endoplasmic reticulum stress in the rat placenta.PloS one · 2015Article
- A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase.The Korean journal of internal medicine · 2014Article
- Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma.Endocrine-related cancer · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-bromopyruvate (3-BP), a hexokinase (HK) II inhibitor, promotes tumor cell death by inducing endoplasmic reticulum (ER) stress in human hepatocellular carcinoma (HCC) cell lines. Protein disulfide isomerase (PDI) is an essential folding catalyst and attenuates ER stress by folding the misfolded proteins. We examined if PDI is expressed in hypoxic HCC cells, and evaluated its inhibition potentiated HK II inhibitor-induced ER stress in hypoxic HCC cells. HCC apoptotic cell death was assessed by DAPI staining and apoptotic signaling pathways were explored by immunoblot analysis. An in vivo model of HCC was established in C3H mice intradermally with implanted MH134 cells. 3-BP with/without a PDI inhibitor (bacitracin) was subsequently administered. The anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVDs). HCC cells were found to express PDI in a hypoxia-inducible manner. The simultaneous treatment of bacitracin and 3-BP enhanced 3-BP-induced apoptosis. This enhancement was attributed to increased ER stress and JNK activation compared to the cells treated with just 3-BP. In an in vivo model of HCC, tumor growth was significantly suppressed in mice co-treated with bacitracin and 3-BP, and the percentages of apoptotic cells significantly increased and MVDs significantly decreased. These results demonstrated that PDI was induced in hypoxic HCC tissue and that PDI inhibition enhanced HK II inhibitor-induced anti-tumor efficacy synergistically via augmenting ER stress and anti-angiogenesis in vivo. Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs.
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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.