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Iranian Journal of Public Health، جلد ۵۳، شماره ۱۰، صفحات ۲۲۷۹-۲۲۸۹
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عنوان انگلیسی 4-Methyl-N-(Piperidin-1-Ylmethylene) Benzenesulfonamide (PMSA) Promotes Ferroptosis of Tumor Cells by Targeting the KEAP1-NRF2-GPX4 Axis
چکیده انگلیسی مقاله Background: We aimed to investigate the effect of 4-methyl-N-(piperidin-1-ylmethylene) benzenesulfonamide (PMSA) on tumor cell proliferation, migration, ferroptosis, and the potential molecular mechanism of ferroptosis in tumor cells. Methods: PMSA was produced in the marine biomedical research institute of Guangdong Medical University (Zhanjiang, China) and used for tumor cells treatment. MTT and cell colony formation assays were used to measure the inhibition of tumor cell proliferation, the scratch assay was used to identified the suppression of tumor cell migration, the death of tumor cells was measured by Annexin-V-FITC/PI staining, the level of ferroptosis-relative lipid ROS in tumor cells was measured by flow cytometry and MDA detection kit, and the expression of ferroptosis-relative protein was measured by Western blot. The Discovery Studio system was used for molecular docking and the binding ability was measured by cellular thermal shift assay. Results: The PMSA we produced inhibited tumor cell proliferation, colony formation, migration and triggered cell death, and Fer-1 could reverse these effects. The amount of ROS and MDA levels in tumor cells was also markedly raised by PMSA. PMSA treatment significantly reduced the expression of SLC7A11/XCT, NRF2, and GPX4 in tumor cells. The phosphorylation level of NRF2 was also decreased. Through molecular docking, it was discovered that PMSA could bind to NRF2 and thereby block its activity. Conclusion: The KEAP1-NRF2-GPX4 axis was the target of PMSA’s anti-tumor action, which results in ferroptosis of tumor cells. This demonstrated that the compound has the potential to be used as a candidate for anti-tumor drugs.
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نویسندگان مقاله | Bingchun Sun
The Marine Biomedical Research Institute, Department of Gynaecology and Obstetrics of Affiliated Hospital, Guang-dong Medical University, Zhanjiang 524001, Guangdong, China


| Guangyu Zhao
The Marine Biomedical Research Institute, Department of Gynaecology and Obstetrics of Affiliated Hospital, Guang-dong Medical University, Zhanjiang 524001, Guangdong, China


| Ligang Zhang
School of Medicine, Foshan University, Foshan 528225, Guangdong, China


| Binhua Wu
The Marine Biomedical Research Institute, Department of Gynaecology and Obstetrics of Affiliated Hospital, Guangdong Medical University, Zhanjiang 524001, Guangdong, China


| Jianji Hou
The Marine Biomedical Research Institute, Department of Gynaecology and Obstetrics of Affiliated Hospital, Guangdong Medical University, Zhanjiang 524001, Guangdong, China
نشانی اینترنتی https://ijph.tums.ac.ir/index.php/ijph/article/view/34945
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