Abstract
Selenium-containing agents showed novel anticancer activity by triggering pro-oxidative mechanism. Studies confirmed that methylseleninic acid (MeSe) displayed broad-spectrum anti-tumor activity against kinds of human cancers. However, the anticancer effects and mechanism of MeSe against human glioma growth have not been explored yet. Herein, the present study showed that MeSeA dose-dependently inhibited U251 and U87 human glioma cells growth in vitro. Flow cytometry analysis indicated that MeSe induced significant U251 cells apoptosis with a dose-dependent manner, followed by the activation of caspase-7, caspase-9 and caspase-3. Immunofluorescence staining revealed that MeSe time-dependently caused reactive oxide species (ROS) accumulation and subsequently resulted in oxidative damage, as convinced by the increased phosphorylation level of Ser428-ATR, Ser1981-ATM, Ser15-p53 and Ser139-histone. ROS inhibition by glutathione (GSH) effectively attenuated MeSe-induced ROS generation, oxidative damage, caspase-3 activation and cytotoxicity, indicating that ROS was an upstream factor involved in MeSe-mediated anticancer mechanism in glioma. Importantly, MeSe administration in nude mice significantly inhibited glioma growth in vivo by inducing apoptosis through triggering oxidative damage. Taken together, our findings validated the possibility that MeSe as a selenium-containing can act as potential tumor chemotherapy agent for therapy of human glioma.
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This study was supported by Medical Health Science and Technology Project of Shandong Province (202302021265), Key Research and Development Project of Linyi City (2023YX0008) and Natural Science Foundation of Shandong (ZR2022MH106).
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XJ, XY and JL designed the study. WC. XT, QL and PD prepared and revised the manuscript. QL, XZ, JC and ZX contributed to the quality assessment, data analysis, and interpretation of the data. All authors revised the manuscript and approved the submitted version.
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Chen, W., Hao, P., Song, Q. et al. Methylseleninic acid inhibits human glioma growth in vitro and in vivo by triggering ROS-dependent oxidative damage and apoptosis. Metab Brain Dis 39, 625–633 (2024). https://doi.org/10.1007/s11011-024-01344-5
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DOI: https://doi.org/10.1007/s11011-024-01344-5