Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells
Abstract Background Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01382-z |
| _version_ | 1797273829875122176 |
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| author | Shengjie Peng Guodong Chen K. N. Yu Yue Feng Lele Zhao Miaomiao Yang Wei Cao Waleed Abdelbagi Ahmed Almahi Mingyu Sun Yuan Xu Ye Zhao Cheng Cheng Fengqin Zhu Wei Han |
| author_facet | Shengjie Peng Guodong Chen K. N. Yu Yue Feng Lele Zhao Miaomiao Yang Wei Cao Waleed Abdelbagi Ahmed Almahi Mingyu Sun Yuan Xu Ye Zhao Cheng Cheng Fengqin Zhu Wei Han |
| author_sort | Shengjie Peng |
| collection | DOAJ |
| description | Abstract Background Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3. Methods CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3. Results We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment. Conclusion Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application. Graphical Abstract Video Abstract |
| first_indexed | 2024-03-07T14:49:50Z |
| format | Article |
| id | doaj.art-ab656864d2554883bb46cb26951e27c9 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-07T14:49:50Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-ab656864d2554883bb46cb26951e27c92024-03-05T19:47:11ZengBMCCell Communication and Signaling1478-811X2024-02-0122111410.1186/s12964-023-01382-zSynergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cellsShengjie Peng0Guodong Chen1K. N. Yu2Yue Feng3Lele Zhao4Miaomiao Yang5Wei Cao6Waleed Abdelbagi Ahmed Almahi7Mingyu Sun8Yuan Xu9Ye Zhao10Cheng Cheng11Fengqin Zhu12Wei Han13Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesDepartment of Physics, City University of Hong KongAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesTeaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical UniversityInstitute of Plasma Physics, Hefei Institutes of Physical Science, Chinese Academy of SciencesHefei Cancer Hospital, Chinese Academy of SciencesAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAbstract Background Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3. Methods CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3. Results We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment. Conclusion Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application. Graphical Abstract Video Abstracthttps://doi.org/10.1186/s12964-023-01382-zNon-thermal plasmaFerroptosisLung cancerRSL3 clinical application |
| spellingShingle | Shengjie Peng Guodong Chen K. N. Yu Yue Feng Lele Zhao Miaomiao Yang Wei Cao Waleed Abdelbagi Ahmed Almahi Mingyu Sun Yuan Xu Ye Zhao Cheng Cheng Fengqin Zhu Wei Han Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells Cell Communication and Signaling Non-thermal plasma Ferroptosis Lung cancer RSL3 clinical application |
| title | Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells |
| title_full | Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells |
| title_fullStr | Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells |
| title_full_unstemmed | Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells |
| title_short | Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells |
| title_sort | synergism of non thermal plasma and low concentration rsl3 triggers ferroptosis via promoting xct lysosomal degradation through ros ampk mtor axis in lung cancer cells |
| topic | Non-thermal plasma Ferroptosis Lung cancer RSL3 clinical application |
| url | https://doi.org/10.1186/s12964-023-01382-z |
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