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 inCancers Vol. 16; no. 6; p. 1178
Main Authors Al-Marsoummi, Sarmad, Mehus, Aaron A, Garrett, Scott H, Sens, Donald A, Somji, Seema
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 17.03.2024
MDPI
Subjects
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
United Kingdom > UK
England
United States > US
UROtsa
bladder cancer
retinoids
arsenite
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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.
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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Issue 6
Keywords UROtsa
bladder cancer
retinoids
arsenite
Language English
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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...
SourceID pubmedcentral
proquest
gale
crossref
pubmed
SourceType Open Access Repository
Aggregation Database
Index Database
StartPage 1178
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
Volume 16
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