The Effect of Retinoic Acid on Arsenite-Transformed Malignant UROtsa Bladder Cancer Cells: In Vitro Model of Basal Muscle-Invasive Bladder Cancer
Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressiv...
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Published in | Cancers Vol. 16; no. 6; p. 1178 |
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Language | English |
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Abstract | Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival. |
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AbstractList | This study explores the potential use of retinoic acid in treating a severe form of bladder cancer, known as basal muscle-invasive bladder cancer (MIBC), which is among the deadliest cancers in the United States of America. All-trans retinoic acid (tretinoin), commonly used in the differentiation therapy of blood cancer, is investigated in this study for its efficacy against MIBC. By treating bladder cancer cells with tretinoin, the study aimed to determine whether it could diminish the aggressive behavior of these cells. The findings show promising results, suggesting that tretinoin can indeed make the basal muscle cancer cells less aggressive by reducing cell proliferation and increasing differentiation markers. This research could lead to new treatment approaches that improve survival chances for patients with basal muscle-invasive bladder cancer. Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival. Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival. This study explores the potential use of retinoic acid in treating a severe form of bladder cancer, known as basal muscle-invasive bladder cancer (MIBC), which is among the deadliest cancers in the United States of America. All-trans retinoic acid (tretinoin), commonly used in the differentiation therapy of blood cancer, is investigated in this study for its efficacy against MIBC. By treating bladder cancer cells with tretinoin, the study aimed to determine whether it could diminish the aggressive behavior of these cells. The findings show promising results, suggesting that tretinoin can indeed make the basal muscle cancer cells less aggressive by reducing cell proliferation and increasing differentiation markers. This research could lead to new treatment approaches that improve survival chances for patients with basal muscle-invasive bladder cancer. Simple SummaryThis study explores the potential use of retinoic acid in treating a severe form of bladder cancer, known as basal muscle-invasive bladder cancer (MIBC), which is among the deadliest cancers in the United States of America. All-trans retinoic acid (tretinoin), commonly used in the differentiation therapy of blood cancer, is investigated in this study for its efficacy against MIBC. By treating bladder cancer cells with tretinoin, the study aimed to determine whether it could diminish the aggressive behavior of these cells. The findings show promising results, suggesting that tretinoin can indeed make the basal muscle cancer cells less aggressive by reducing cell proliferation and increasing differentiation markers. This research could lead to new treatment approaches that improve survival chances for patients with basal muscle-invasive bladder cancer.AbstractBladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival. |
Audience | Academic |
Author | Sens, Donald A Garrett, Scott H Mehus, Aaron A Somji, Seema Al-Marsoummi, Sarmad |
AuthorAffiliation | Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202, USA |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38539513$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1097/MOU.0000000000000641 10.1158/1078-0432.CCR-03-0756 10.1101/2023.08.19.553961 10.1111/bjh.18187 10.1038/nrurol.2014.129 10.1186/1477-7819-12-130 10.1038/srep38531 10.1016/S0936-6555(05)80778-2 10.3390/ijms22073510 10.3390/ijms24119149 10.3389/fsurg.2022.860663 10.1371/journal.pone.0207877 10.1186/s12935-020-01235-6 10.1371/journal.pone.0011513 10.1007/BF02256129 10.1038/nrc.2017.103 10.1016/j.tox.2008.03.020 10.1016/j.ccr.2014.01.009 10.1038/s41598-020-66747-7 10.1016/j.eururo.2015.08.034 10.1038/35106036 10.3390/cancers15143535 10.1101/cshperspect.a014241 10.1289/ehp.10279 10.1016/j.ccr.2014.01.026 10.1016/0092-8674(92)90479-V 10.1016/j.taap.2019.04.021 10.1007/s002400050084 10.1074/jbc.M201885200 10.1093/aje/kwh054 10.1371/journal.pone.0036669 10.1016/j.mam.2014.12.003 10.1093/aje/kwg281 10.1093/toxsci/kfh086 10.3390/jcm9082494 10.3389/fgene.2022.1065320 10.1093/jnci/djw099 |
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Keywords | UROtsa bladder cancer retinoids arsenite |
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Snippet | Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer... This study explores the potential use of retinoic acid in treating a severe form of bladder cancer, known as basal muscle-invasive bladder cancer (MIBC), which... Simple SummaryThis study explores the potential use of retinoic acid in treating a severe form of bladder cancer, known as basal muscle-invasive bladder cancer... |
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SubjectTerms | Acids Antiacne agents Apoptosis Arsenic compounds Arsenite Bladder cancer c-Myc protein Cancer Cancer cells Care and treatment Cell differentiation Cell growth Cell proliferation Cell viability Down-regulation Enzymes Flow cytometry GATA-3 protein Gentian violet Health aspects Invasiveness Malignancy Medical prognosis mRNA Myc protein Oncology, Experimental Retinoic acid Retinoic acid receptors Retinoid X receptors Retinoids RNA Urothelial cancer Vitamin A |
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Title | The Effect of Retinoic Acid on Arsenite-Transformed Malignant UROtsa Bladder Cancer Cells: In Vitro Model of Basal Muscle-Invasive Bladder Cancer |
URI | https://www.ncbi.nlm.nih.gov/pubmed/38539513 https://www.proquest.com/docview/2996469843 https://search.proquest.com/docview/3014003738 https://pubmed.ncbi.nlm.nih.gov/PMC10969336 |
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