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  3. Exogenous carbon monoxide promotes GPX4-dependent ferroptosis through ROS/GSK3β axis in non-small cell lung cancer

Exogenous carbon monoxide promotes GPX4-dependent ferroptosis through ROS/GSK3β axis in non-small cell lung cancer

  • Cell Death Discov. 2024 Jan 23;10(1):42. doi: 10.1038/s41420-023-01743-0.
Wei Cao # 1 2 3,  Mingyu Sun # 2,  K N Yu 4 5,  Lele Zhao 2,  Yue Feng 2,  Chunhua Tan 2,  Miaomiao Yang 1,  Ying Wang 1 3,  Fengqin Zhu 1 3,  Lianjun Chen 6,  Lili Nie 1 3,  Ye Zhao 2,  Guodong Chen 7 8 9,  Wei Han 10 11 12 13
Affiliations

Affiliations

  • 1 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, 230031, Hefei, P. R. China.
  • 2 Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 230031, Hefei, P.R. China.
  • 3 Hefei Cancer Hospital, Chinese Academy of Sciences, 230031, Hefei, P. R. China.
  • 4 Department of Physics, City University of Hong Kong, 999077, Hong Kong, P. R. China.
  • 5 State Key Laboratory in Marine Pollution, City University of Hong Kong, 999077, Hong Kong, P. R. China.
  • 6 School of Biology, Food and Environment, Hefei University, 230031, Hefei, P. R. China.
  • 7 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, 230031, Hefei, P. R. China. chengd@cmpt.ac.cn.
  • 8 Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 230031, Hefei, P.R. China. chengd@cmpt.ac.cn.
  • 9 Hefei Cancer Hospital, Chinese Academy of Sciences, 230031, Hefei, P. R. China. chengd@cmpt.ac.cn.
  • 10 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, 230031, Hefei, P. R. China. hanw@hfcas.ac.cn.
  • 11 Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 230031, Hefei, P.R. China. hanw@hfcas.ac.cn.
  • 12 Hefei Cancer Hospital, Chinese Academy of Sciences, 230031, Hefei, P. R. China. hanw@hfcas.ac.cn.
  • 13 Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 215006, Suzhou, P. R. China. hanw@hfcas.ac.cn.
  • # Contributed equally.
PMID: 38263152 DOI: 10.1038/s41420-023-01743-0
Abstract

The gas therapy is drawing increasing attention in the treatment of many diseases including Cancer. As one of gas signaling molecules, carbon monoxide (CO) has been proved to exert anti-cancer effects via triggering multiple cell death types, such as Autophagy, Apoptosis and necrosis. Here, we showed that low concentration CO delivered from CO-releasing molecule 3 (CORM-3) effectively induced Ferroptosis, known as a novel proinflammatory programmed cell death, in vitro and in vivo. Mechanistically, we found that CO triggered Ferroptosis by modulating the ROS/GSK3β/GPX4 signaling pathway, resulting in the accumulation of lipid hydroperoxides and the occurrence of Ferroptosis. We think our findings provide novel insights into the anti-cancer mechanisms of CO, and suggest that CO could potentially be exploited as a novel Ferroptosis inducer for Cancer treatment in the future.

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