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Mefloquine enhances radiosensitivity of glioma cells through ROS-dependent apoptosis
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A. Wang   , Y. Miao , A. Guo , X. Hu , Z. Ding , X. Zhang |
| Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, P.R. China , zhangxiaohong@nuaa.edu.cn |
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Abstract: (14 Views) |
Background: Radiosensitizers enhance the effectiveness of radiation therapy by reducing the radio-resistance of cancer cells. A key advantage of traditional drug repositioning over the development of new drugs is the rapid repurposing of existing medications for new therapeutic applications. Mefloquine, a classical antimalaria drug, has also demonstrated anti-tumor activity through various mechanisms. The goal of this study is to investigate the potential of mefloquine as a radiosensitizer on gliomas. Materials and Methods: Gliomas were pre-treated with mefloquine prior to X-ray irradiation. The radiosensitization of mefloquine on these cells was first estimated using a clonogenic formation assay. To determine the mode of cell death, apoptosis and autophagy were measured in U251 gliomas at different intervals after mefloquine-mediated radiosensitization. Additionally, intracellular levels of reactive oxygen species and calcium ions were measured to explore the molecular mechanism during mefloquine-mediated radiosensitization. Results: Mefloquine was demonstrated to present a notable radiosensitizing effect on gliomas. However, the enhancement of protective autophagy diminished the radiosensitizing effect on the first day following combined treatment with mefloquine and X-rays. From the third day onward, the radiosensitization became more pronounced, attributed to a reduction in protective autophagy and an increase in apoptosis. Further study revealed that the increased apoptosis during mefloquine-mediated radiosensitization was dependent on intracellular reactive oxygen species levels, as the apoptotic response was inhibited by glutathione. Conclusion: Our findings demonstrate that mefloquine can elevate the radiosensitivity of gliomas through reactive oxygen species-dependent apoptosis. |
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| Keywords: Radiation-sensitizing agents, mefloquine, glioma cells, apoptosis, reactive oxygen species. |
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Full-Text [PDF 1474 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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