Studying ferroptosis and iron metabolism pre- and post-radiotherapy treatment in breast cancer patients

Journal of the Egyptian National Cancer Institute
Sanaa A. El-Benhawy1, Ibrahim G. Abdelrhman2, Nayera Sadek3, Enayat I Fahmy1, Ahmed Amin Abogabal4, Hossam M. El-Masry5, Sally A M Saleh3, Ola A Sakr6, Mona Nagy Elwany7, Maha A. Rabie8
1Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
2Radiology and Medical Imaging Department, Faculty of Applied Health Sciences, October 6 University, Cairo, Egypt
3Hematology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
4Radiation Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt
5Medical Laboratory Specialist, Baheya Foundation for Early Detection and Treatment of Breast Cancer, Cairo, Egypt
6Cancer Management and Research Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
7Pathology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
8Medical Laboratory Department, Faculty of Applied Health Science Technology, Pharos University, Alexandria, Egypt

Tóm tắt

Abstract Background Radiotherapy (RT) is an important part of the treatment of many tumors. Radiotherapy causes oxidative damage in all cellular compartments, including lipid membrane, on a random basis. Toxic lipid peroxidation accumulation has only lately been linked to a regulated type of cell death known as ferroptosis. Iron is required for ferroptosis sensitization in cells. Aim of the work This work aimed to study ferroptosis and iron metabolism before and after RT in BC patients. Subjects and methods Eighty participants were included divided into two main groups: group I: 40 BC patients treated with RT. Group II: 40 healthy volunteers’ age and sex matched as control group. Venous blood samples were collected from BC patients (prior to and after RT) and healthy controls. Glutathione (GSH), malondialdehyde (MDA), serum iron levels and % of transferrin saturation were measured by colorimetric technique. Ferritin, ferroportin, and prostaglandin-endoperoxide synthase 2 (PTGS2) levels were assessed by ELISA. Results Serum ferroportin, reduced glutathione, and ferritin showed significant decrease after radiotherapy in comparison to before radiotherapy. However, there was significant increase in serum PTGS2, MDA, % of transferrin saturation and iron levels after radiotherapy in comparison to before radiotherapy. Conclusion Radiotherapy induced ferroptosis in breast cancer patients as a new cell death mechanism and PTGS2 is a biomarker of ferroptosis. Iron modulation is a useful approach for the treatment of BC especially if combined with targeted therapy and immune-based therapy. Further studies are warranted to be translated into clinical compounds.

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Journal of the Egyptian National Cancer Institute

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