Vitamin A rich diet diminishes early urothelial carcinogenesis by altering retinoic acid signaling

Zupančič, Daša (author), Korać-Prlić, Jelena (author), Erdani-Kreft, Mateja (author), Franković, Lucija (author), Vilović, Katarina (author), Jeruc, Jera (author), Romih, Rok (author), Terzić, Janoš (author)

Urinary bladder cancer is one of the leading malignancies worldwide, with the highest recurrence rates. A diet rich in vitamin A has proven to lower the risk of cancer, yet the molecular mechanisms underlying this effect are unknown. We found that vitamin A decreased urothelial atypia and apoptosis during early bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Vitamin A did not alter urothelial cell desquamation, differentiation, or proliferation rate. Genes like Wnt5a, involved in retinoic acid signaling, and transcription factors Pparg, Ppara, Rxra, and Hoxa5 were downregulated, while Sox9 and Stra6 were upregulated in early urothelial carcinogenesis. When a vitamin A rich diet was provided during BBN treatment, none of these genes was up- or downregulated; only Lrat and Neurod1 were upregulated. The lecithin retinol acyltransferase (LRAT) enzyme that produces all-trans retinyl esters was translocated from the cytoplasm to the nuclei in urothelial cells as a consequence of BBN treatment regardless of vitamin A rich diet. A vitamin A-rich diet altered retinoic acid signaling, decreased atypia and apoptosis of urothelial cells, and consequently diminished early urothelial carcinogenesis.

• Language: English
• Keywords: urinary bladder, early carcinogenesis, vitamin A, retinoic acid signaling, apoptosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 19 str.
• Numbering: Vol. 12, iss. 7, art. 1712
• PID: 20.500.12556/RUL-133685
• UDC: 616-006
• ISSN on article: 2072-6694
• DOI: 10.3390/cancers12071712
• COBISS.SI-ID: 21184515
• Publication date in RUL: 09.12.2021

Record is a part of a journal

• Title: Cancers
• Shortened title: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.07.2020

Secondary language

• Language: Slovenian
• Keywords: mehur, early carcinogenesis, vitamin A