ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1704804
Immunomodulatory Effect of Betulin and Its Derivatives on IL-6 Expression in Colorectal Cancer Cell Lines and Molecular Docking Insights
Provisionally accepted
- 1Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
- 2Silesia LabMed, Centre for Research and Implementation, Medical University of Silesia, Katowice, Poland
- 3Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
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Purpose: This study investigated the immunomodulatory and therapeutic potential of betulin and its derivatives (EB5 and ECH147) in colorectal cancer (CRC), focusing on their effects on IL-6 expression at the molecular level and their possible application as diagnostic and therapeutic tools. Methods: Human CRC cell lines (HT-29, RKO, SW1116) and normal colonocytes (CCD-841CoN) were treated with betulin, EB5, ECH147, cisplatin, and 5-fluorouracil (10 μg/mL) for 2, 8, and 24 hours. IL-6 mRNA levels were measured by RT-qPCR in real time, and IL-6 protein was quantified using a proximity ligation immunoassay. Molecular docking was performed using IL-6 structure (PDB ID: 1ALU). Statistical significance was evaluated using Kruskal–Wallis and post hoc rank tests. Results: IL-6 expression was undetectable in HT-29 and RKO cells, both harboring the BRAFV600E mutation. ECH147 and EB5 derivatives significantly decreased IL-6 mRNA and protein levels in SW1116 and CCD-841CoN cells at 8 and 24 hours. Molecular docking analysis revealed that ECH147 formed a stable hydrogen bond, suggesting direct binding. Conclusion: Structural modification of betulin enhances its molecular therapeutic activity, with phosphonate derivative ECH147 showing the strongest decrease in IL-6 levels. These findings suggest that IL-6 downregulation can serve as a molecular biomarker for drug efficacy, while ECH147 represents a promising candidate for targeted molecular therapy in CRC. This dual diagnostic–therapeutic approach highlights the potential of betulin derivatives in advancing precision medicine for IL-6–mediated pathways.
Keywords: Colorectal cancer1, IL-62, betulin3, derivatives4, mRNA5, Protein6
Received: 13 Sep 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Madej, Halama, Chrobak, Bębenek and Gola. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Marcel Madej, marcel.madej@sum.edu.pl
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