Abstract
Cervical cancer is among the most frequently observed cancer types in females. New therapeutic targets are needed because of the side impacts of existing cancer drugs and the inadequacy of treatment methods. Thioredoxin reductase 1 (TrxR1) is often overexpressed in many cancer cells, and targeting TrxR1 has become an attractive target for cancer therapy. This study investigated the anticancer impacts of diffractaic and vulpinic acids, lichen secondary metabolites, on the cervical cancer HeLa cell line. XTT findings demonstrated showed that diffractaic and vulpinic acids suppressed the proliferation of HeLa cells in a dose- and time-dependent manner and IC50 values were 22.52 μg/ml and 66.53 μg/ml at 48 h, respectively. Each of these lichen metabolites significantly suppressed migration. Diffractaic acid showed an increase in both the BAX/BCL2 ratio by qPCR analysis and the apoptotic cell population via flow cytometry analysis on HeLa cells. Concerning vulpinic acid, although it decreased the BAX/BCL2 ratio in this cells, it increased apoptotic cells according to the flow cytometry analysis results. Diffractaic and vulpinic acids significantly suppressed TrxR1 enzyme activity rather than the gene and protein expression levels in HeLa cells. This research demonstrated for the first time, that targeting TrxR1 with diffractaic and vulpinic acids was an effective therapeutic strategy for treating cervical cancer.
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The data supporting the findings of the present research are available on request from the corresponding author upon reasonable request.
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Acknowledgements
We would like to thank Dr. Harun Budak at Atatürk University and Dr. Ahmet Altay at Erzincan Binali Yıldırım University for their technical support.
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The Coordination Unit of Scientific Research Project of Atatürk University (ATAUNI-BAP) provided financial support for the present work (Project number: TTU-2021–9285).
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Conceived and designed the experiments: Dr. Büşra Budak (BB), Dr. Şeyda Nur Kalın (ŞNK), and Dr. Ömer Erkan Yapça (ÖEY). Performed the experiments: ŞNK and BB. Analyzed the data: ŞNK and BB. Contributed reagents/materials/analysis tools: ÖEY, ŞNK, and BB. Wrote the paper: ŞNK. All authors read and approved the manuscript’s final version. The authors declare that all data were generated in-house and that no paper mill was used.
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Budak, B., Kalın, Ş.N. & Yapça, Ö.E. Antiproliferative, antimigratory, and apoptotic effects of diffractaic and vulpinic acids as thioredoxin reductase 1 inhibitors on cervical cancer. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1525–1535 (2024). https://doi.org/10.1007/s00210-023-02698-w
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DOI: https://doi.org/10.1007/s00210-023-02698-w