Journal article
Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: mechanisms and therapeutic potential
Cancer treatment and research communications, Vol.42, 100864
01/09/2025
DOI: 10.1016/j.ctarc.2025.100864
PMCID: PMC11846624
PMID: 39813754
Abstract
Clear cell renal cell carcinoma (ccRCC) poses a significant global health challenge as its incidence continues to rise, resulting in a substantial annual mortality rate. Major clinical challenges to current ccRCC treatments include high drug-resistance rates as well as dose-limiting adverse events; underlining the need to identify additional ‘druggable’ targets. TGF-β1, VEGF, and PD-L1 are potential therapeutic targets in ccRCC. This study analyzed their expression in human ccRCC cell lines and patient tumor biopsies. Data obtained from western blotting demonstrated higher levels of TGF-β1 and PD-L1 and lower levels of VEGF in sarcomatoid ccRCC lines compared to non-sarcomatoid ccRCC lines. In patient samples, TGF-β1 was significantly upregulated in both non-sarcomatoid and sarcomatoid ccRCC tumors. It was demonstrated through two assays (cellular thermal shift assay and a size exclusion assay) that methylseleninic acid (MSA) binds specifically and directly to TGF-β1. MSA treatment significantly downregulated TGF-β1, PD-L1, and VEGF in a dose- and time-dependent manner in both non-sarcomatoid and sarcomatoid ccRCC cell lines. Seleno-L-methionine (SLM) treatment in a nude mouse xenograft model showed significant tumor growth inhibition and TGF-β1 downregulation at non-toxic doses. These findings suggest that selenium-mediated downregulation of TGF-β1, PD-L1, and VEGF could be a viable therapeutic strategy for ccRCC.
Details
- Title: Subtitle
- Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: mechanisms and therapeutic potential
- Creators
- Aseel O. Rataan - University of IowaYan Xu - University of IowaSean M. Geary - University of IowaYousef Zakharia - University of IowaEman S. Kamel - University of IowaYoucef M. Rustum - University of IowaAliasger K. Salem - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer treatment and research communications, Vol.42, 100864
- DOI
- 10.1016/j.ctarc.2025.100864
- PMID
- 39813754
- PMCID
- PMC11846624
- NLM abbreviation
- Cancer Treat Res Commun
- ISSN
- 2468-2942
- eISSN
- 2468-2942
- Publisher
- Elsevier Ltd
- Grant note
- National Institute of HealthLyle and Sharon Bighley Chair in Pharmaceutical Sciences grant
We thank Dr. Steven Eliason for providing RCC4 and RCC4/VHL cell lines, Dr. Christopher Stipp for RC2 cell line, Dr. Thai H. Ho for RCJ41T1, RCJ41T2 and RCJ41M cell lines and Dr. Marston Linehan for providing UOK127 cell line. This work was supported by the National Institute of Health grant P30CA086862 and the Lyle and Sharon Bighley Chair in Pharmaceutical Sciences grant.
- Language
- English
- Date published
- 01/09/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Internal Medicine
- Record Identifier
- 9984773416502771
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