1. Academic Validation
  2. Hemin enhances radiosensitivity of lung cancer cells through ferroptosis

Hemin enhances radiosensitivity of lung cancer cells through ferroptosis

  • Exp Cell Res. 2022 Jan 1;410(1):112946. doi: 10.1016/j.yexcr.2021.112946.
Waleed Abdelbagi Almahi 1 K N Yu 2 Fathelrahman Mohammed 3 Peizhong Kong 4 Wei Han 5
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, Hefei, 230031, People's Republic of China; Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China; Sudan Atomic Energy Commission, Nuclear Applications in Biological Sciences Institute, Radiobiology and Cancer Researches Department, Khartoum 11111, P.O Box 3001, Sudan. Electronic address: [email protected].
  • 2 Department of Physics, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, 999077, Hong Kong, People's Republic of China; State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, 999077, Hong Kong, People's Republic of China. Electronic address: [email protected].
  • 3 CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, Anhui, China. Electronic address: [email protected].
  • 4 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People's Republic of China. Electronic address: [email protected].
  • 5 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People's Republic of China; Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, People's Republic of China. Electronic address: [email protected].
Abstract

The principle underlying radiotherapy is to kill Cancer cells while minimizing the harmful effects on non-cancer cells, which has still remained as a major challenge. In relation, Ferroptosis has recently been proposed as a novel mechanism of radiation-induced cell death. In this study, we investigated and demonstrated the role of Hemin as an iron overloading agent in the generation of Reactive Oxygen Species (ROS) induced by ionizing radiation in lung Cancer and non-cancer cells. It was found that the presence of Hemin in irradiated lung Cancer cells enhanced the productivity of initial ROS, resulting in lipid peroxidation and subsequent Ferroptosis. We observed that application of Hemin as a co-treatment increased the activity of GPx4 degradation in both Cancer and normal lung cells. Furthermore, Hemin protected normal lung cells against radiation-induced cell death, in that it suppressed ROS after radiation, and boosted the production of bilirubin which was a lipophilic ROS antioxidant. In addition, we demonstrated significant FTH1 expression in normal lung cells when compared to lung Cancer cells, which prevented iron from playing a role in increasing IR-induced cell death. Our findings demonstrated that Hemin had a dual function in enhancing the radiosensitivity of Ferroptosis in lung Cancer cells while promoting cell survival in normal lung cells.

Keywords

Bilirubin; FTH1; Ferroptosis; GPx4; Hemin; ROS; Radiosensitivity.

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