Abstract
Quercetin has been documented to possess a multitude of pharmacological effects, encompassing antioxidant, antiviral, antimicrobial, and anti-inflammatory properties. Nevertheless, the exact molecular mechanisms responsible for the anti-tumor properties of quercetin remain to be fully explicated. To this end, quercetin was administered to gastric cancer cells (in vitro) AGS and MKN45, as well as BALB/c mice (in vivo). The proliferation ability of cells was evaluated using cholecystokinin octapeptide (CCK-8) and colony formation assays. The evaluation of ferroptosis involved the measurement of iron, malondialdehyde (MDA), and lipid reactive oxygen species. Autophagy and apoptosis were evaluated using immunofluorescence staining, western blotting, and flow cytometry analysis. Our findings indicate that quercetin significantly inhibited cell viability and tumor volume compared to the control group. Additionally, quercetin was found to decrease glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels while suppressing beclin1 and LC3B levels in cancer cells. Remarkably, the utilization of siATG5 was found to reverse all the aforementioned effects of quercetin. Ultimately, the effects of quercetin on gastric cancer were validated. In summary, our findings provide evidence that quercetin facilitates autophagy-mediated ferroptosis in gastric cancer.
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National Natural Science Foundation of China (81870453); Transverse Connection Research project of Shandong university (1520020012).
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All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript; JH, JNL and JC conducted the experiments, JNL and JC wrote and revised the manuscript.
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Huang, J., Chen, J. & Li, J. Quercetin promotes ATG5-mediating autophagy-dependent ferroptosis in gastric cancer. J Mol Histol 55, 211–225 (2024). https://doi.org/10.1007/s10735-024-10186-5
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DOI: https://doi.org/10.1007/s10735-024-10186-5