Abstract
Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking β‐catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/β‐catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by grants from the Hunan University of Chinese Medicine graduate innovation project (2022CX67), the key project of first-class discipline of integrated Traditional Chinese and Western Medicine (2021ZXYJH02), and the Key Discipline of Basic Medicine, Hunan University of Chinese Medicine (202302).
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YC and YL conceived and designed the research. JX, HW, and WX performed experiments. JX analyzed and plotted data. JX and YL prepared Figs. 1–5. YC, YL, and JX wrote and revised the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Xie, J., Wang, H., Xie, W. et al. Gallic acid promotes ferroptosis in hepatocellular carcinoma via inactivating Wnt/β-catenin signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2437–2445 (2024). https://doi.org/10.1007/s00210-023-02770-5
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DOI: https://doi.org/10.1007/s00210-023-02770-5