ArticleMolecular cancer2011
Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells.
Article in Molecular cancer, 2011. 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.
- Transglutaminase 7 Silencing Inhibits Proliferation and Modulates Inflammatory and Apoptotic Markers in Testicular Germ Cell Tumors.Oncology research · 2025Article
- Role of transglutaminase 2 in promoting biglycan synthesis in idiopathic gingival fibromatosis.BMC oral health · 2024Article
- Deletion of Tgm2 suppresses BMP-mediated hepatocyte-to-cholangiocyte metaplasia in ductular reaction.Cell proliferation · 2024Article
- Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid.Cell death & disease · 2023Article
- Specificity Proteins (Sp) and Cancer.International journal of molecular sciences · 2023Review
- MiR-767-3p promotes the progression of hepatocellular carcinoma via targeting CASP-3/-9.American journal of translational research · 2023Article
- A Central Contribution of TG2 Activity to the Antiproliferative and Pro-Apoptotic Effects of Caffeic Acid in K562 Cells of Human Chronic Myeloid Leukemia.International journal of molecular sciences · 2022Article
- Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis.Biomedicines · 2022Article
- Review
- Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53.Oncogene · 2021Article
- Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target.Molecular carcinogenesis · 2019Article
- Arachidonic acid suppresses hepatic cell growth through ROS-mediated activation of transglutaminase.FEBS open bio · 2018Article
- Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes.EBioMedicine · 2017Article
- Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death.Cell death & disease · 2016Review
- Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells.Cell death & disease · 2015Article
- Non-alcoholic steatohepatitis and hepatocellular carcinoma: implications for lycopene intervention.Nutrients · 2013Review
- Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.The Journal of biological chemistry · 2013Article
- The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2013Article
- The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells.PloS one · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma has a high mortality rate due to its rate of recurrence. Acyclic retinoid prevents recurrence of hepatocellular carcinoma in patients after surgical removal of their primary tumors by inducing apoptosis in hepatocellular carcinoma cells, although the molecular mechanisms of action are not understood.
methodsHuman hepatocellular carcinoma cells in culture, as well as nude mice transplanted with hepatocellular carcinoma cells and rats given with N-diethylnitrosamine were treated with acyclic retinoid. Changes in activated caspase 3 and transglutaminase 2 (TG2) levels, Sp1 cross-linking and its activities, expression of epidermal growth factor receptor, and apoptotic levels were measured.
resultsAcyclic retinoid simultaneously stimulated the activation of caspase 3, and the expression, nuclear localization and crosslinking activity of TG2, resulting in crosslinking and inactivation of the transcription factor, Sp1, thereby reducing expression of epidermal growth factor receptor and cell death in three hepatocellular carcinoma cell lines. These effects were partially restored by a caspase inhibitor, transfection of antisense TG2, restoration of functional Sp1, or an excess of epidermal growth factor. Nuclear expression of TG2 and crosslinked Sp1, as also activated caspase 3 were found in both hepatocellular carcinoma cells transplanted into nude mice and cancerous regions within the liver in N-diethylnitrosamine-induced hepatocarcinogenesis model in rats, following treatment of animals with acyclic retinoid.
conclusionsTreatment with acyclic retinoid produces a dual activation of caspase 3 and TG2 induced apoptosis of hepatocellular carcinoma cells via modification and inactivation of Sp1, resulting in reduced expression of epidermal growth factor receptor.
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