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The influence of betulin and its derivatives on the expression of TNF and its receptors in RPTEC cells
1
Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
2
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
Corresponding author
Joanna Gola
Zakład Biologii Molekularnej, Wydział Nauk Farmaceutycznych w Sosnowcu ŚUM, ul. Jedności 8, 41-200 Sosnowiec
Zakład Biologii Molekularnej, Wydział Nauk Farmaceutycznych w Sosnowcu ŚUM, ul. Jedności 8, 41-200 Sosnowiec
Ann. Acad. Med. Siles. 2025;79:237-245
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Despite their promising anticancer properties, betulin derivatives may have serious side effects, including nephrotoxicity. Tumor necrosis factor (TNF) and its receptors may play crucial roles in renal cells’ reaction to these compounds. The aim of this study was to examine the effect of the derivatives EB5 and ECH147 on renal cell expression of TNF and its receptors.
Material and methods:
Human renal proximal tubule epithelial cells (RPTECs) were treated with betulin, EB5, and ECH147, as well as cisplatin and 5-fluorouracil. The transcript levels of the genes TNF, TNFR1, and TNFR2 were assessed using real-time RT-qPCR. Protein concentrations in the culture media were determined using ELISA.
Results:
The transcriptional activity of the gene TNF was induced in cells treated with 0.5 µg/mL betulin or ECH147. Similar changes in transcriptional activity were observed for TNFR1. Betulin and its derivatives strongly inhibited the expression of TNFR2. No TNF or sTNFR2 proteins were detected in the culture media. EB5 downregulated sTNFR1 release in comparison with the other compounds.
Conclusions:
EB5 at low concentrations may be less harmful to renal cells. The lower toxicity of EB5 may be a result of the altered expression of TNF and its receptors.
Despite their promising anticancer properties, betulin derivatives may have serious side effects, including nephrotoxicity. Tumor necrosis factor (TNF) and its receptors may play crucial roles in renal cells’ reaction to these compounds. The aim of this study was to examine the effect of the derivatives EB5 and ECH147 on renal cell expression of TNF and its receptors.
Material and methods:
Human renal proximal tubule epithelial cells (RPTECs) were treated with betulin, EB5, and ECH147, as well as cisplatin and 5-fluorouracil. The transcript levels of the genes TNF, TNFR1, and TNFR2 were assessed using real-time RT-qPCR. Protein concentrations in the culture media were determined using ELISA.
Results:
The transcriptional activity of the gene TNF was induced in cells treated with 0.5 µg/mL betulin or ECH147. Similar changes in transcriptional activity were observed for TNFR1. Betulin and its derivatives strongly inhibited the expression of TNFR2. No TNF or sTNFR2 proteins were detected in the culture media. EB5 downregulated sTNFR1 release in comparison with the other compounds.
Conclusions:
EB5 at low concentrations may be less harmful to renal cells. The lower toxicity of EB5 may be a result of the altered expression of TNF and its receptors.
FUNDING
This research was funded by the Medical University of Silesia, Katowice, Poland (grant no. PCN-1-050/N/1/I).
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
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