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The inhibitory effect of betulinic acid on epithelial–mesenchymal transition pathway in renal cell carcinoma

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Abstract

Renal cancer is the most lethal urological cancer and characterized by high metastasis rate at initial diagnosis and drug resistance to current chemotherapeutics. Betulinic acid is a pentacyclic triterpene with broad biological activity that occurs naturally in variety of plants. Even though the anti-cancer efficacy of betulinic acid have been reported by many studies, the information about the pathways and the molecules which are affected by betulinic acid in renal cancer are limited. Epithelial–mesenchymal transition (EMT) is considered as the initial step of metastasis and contributes to drug resistance of cancer cells. Depending on the role of EMT in cancer progression and drug resistance, targeting EMT may represent an effective strategy in this context. Therefore, we aimed to investigate the anti-metastatic effects of betulinic acid on renal cell carcinoma cells by evaluating two EMT markers, SNAIL-1, and SDC-2. Following the treatment of betulinic acid at determined doses by WST-1 cytotoxicity assay in our previous study, SDC-2 expression level was decreased in both cell lines. Additionally, in correlation with this result, we also found a reduction in SDC-2 and SNAIL-1 protein levels which are measured by ELISA. Furthermore, the migration and invasion capacities were suppressed by betulinic acid treatment in metastatic renal adenocarcinoma ACHN cells. Taken together, our findings indicate that betulinic acid may constitute a potential treatment approach for renal cancer with further investigations.

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Funding

This work was funded by Scientific Research Projects Coordination Unit of Istanbul University. Project No. TSA-2019–35150.

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Authors and Affiliations

  1. Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

    Merve Nur Ataş, Barış Ertuğrul, Bedia Çakmakoğlu & Arzu Ergen

  2. Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey

    Merve Nur Ataş

  3. Department of Biochemistry, Faculty of Medicine, Istanbul Health and Technology University, Istanbul, Turkey

    Elif Sinem İplik

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  1. Merve Nur Ataş
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  2. Barış Ertuğrul
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  3. Elif Sinem İplik
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  4. Bedia Çakmakoğlu
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  5. Arzu Ergen
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Contributions

MNA; Laboratory Analysis and Writing, BE; Laboratory Analysis, ESİ; Statistical Analysis, BÇ; Data Extraction, AE; Study Design and Writing.

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Correspondence to Arzu Ergen.

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Ataş, M.N., Ertuğrul, B., İplik, E.S. et al. The inhibitory effect of betulinic acid on epithelial–mesenchymal transition pathway in renal cell carcinoma. Med Oncol 39, 170 (2022). https://doi.org/10.1007/s12032-022-01775-z

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  • DOI: https://doi.org/10.1007/s12032-022-01775-z

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