Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice

Objective: Our objective was to explore the effect of different fractionation schedule on ferroptosis and pyroptosis biomarkers as new cell death mechanisms induced by IR.Materials and Methods: This study included 40 tumor bearing mice divided into: Group I: Includes 8 untreated tumor-bearing mice....

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Main Authors: Sanaa A El-Benhawy, Samar S Elblehi, Sabbah I Hammoury, Amira A Abo El-Soud
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:Cancer Treatment and Research Communications
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468294222000363
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author Sanaa A El-Benhawy
Samar S Elblehi
Sabbah I Hammoury
Amira A Abo El-Soud
author_facet Sanaa A El-Benhawy
Samar S Elblehi
Sabbah I Hammoury
Amira A Abo El-Soud
author_sort Sanaa A El-Benhawy
collection DOAJ
description Objective: Our objective was to explore the effect of different fractionation schedule on ferroptosis and pyroptosis biomarkers as new cell death mechanisms induced by IR.Materials and Methods: This study included 40 tumor bearing mice divided into: Group I: Includes 8 untreated tumor-bearing mice. Group II: Includes 8 tumor bearing mice exposed to single dose 6 Gy of IR. Group III: Includes 8 tumor bearing mice exposed to 12 Gy in 2 fractions (2 × 6 Gy) of IR. Group IV: Includes 8 tumor bearing mice exposed to 12 Gy in 3 fractions (3 × 4 Gy) of IR. Group V: Includes 8 tumor bearing mice exposed to 8 Gy in 4 fractions (4 × 2 Gy) of IR. IL-1β, IL-18, and GSDMD-CT levels were assessed by ELISA. PTGS2 and ACSL4 expression were assessed by RT-PCR.Results: (2 × 6 Gy) group showed the highest ACSL4 expression followed by (3 × 4 Gy), then (4 × 2 Gy) and finally 6 Gy. (2 × 6 Gy) group resulted in the highest PTGS2 expression followed by (3 × 4 Gy), then 6 Gy, and finally (4 × 2 Gy). MDA significantly increased at (2 × 6 Gy), (3 × 4 Gy), and 6 Gy groups and insignificantly increased at (4 × 2 Gy) group. Iron significantly increased at (2 × 6 Gy), (3 × 4 Gy), and (4 × 2 Gy) groups and insignificantly at 6 Gy. Glutathione was significantly decreased at (2 × 6 Gy), (3 × 4 Gy), and (4 × 2 Gy) groups and insignificantly at 6 Gy. GSDMD-CT, IL-1β, and IL-18 levels significantly reduced in tumor tissues after exposure to IR at all doses.Conclusion: High dose per fraction regimens induce the expression of ferroptosis markers more than low dose per fraction regimen and single dose of IR. IR at all doses induces pyroptotic cell death.
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spelling doaj.art-d59b6c692ddc461f92bf094e0ae426672022-12-22T03:23:31ZengElsevierCancer Treatment and Research Communications2468-29422022-01-0131100545Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing miceSanaa A El-Benhawy0Samar S Elblehi1Sabbah I Hammoury2Amira A Abo El-Soud3Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt; Corresponding author.Pathology Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, EgyptMedical Physics Department, Alexandria Ayadi El mostakbl Oncology Center, Alexandria, EgyptRadiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, EgyptObjective: Our objective was to explore the effect of different fractionation schedule on ferroptosis and pyroptosis biomarkers as new cell death mechanisms induced by IR.Materials and Methods: This study included 40 tumor bearing mice divided into: Group I: Includes 8 untreated tumor-bearing mice. Group II: Includes 8 tumor bearing mice exposed to single dose 6 Gy of IR. Group III: Includes 8 tumor bearing mice exposed to 12 Gy in 2 fractions (2 × 6 Gy) of IR. Group IV: Includes 8 tumor bearing mice exposed to 12 Gy in 3 fractions (3 × 4 Gy) of IR. Group V: Includes 8 tumor bearing mice exposed to 8 Gy in 4 fractions (4 × 2 Gy) of IR. IL-1β, IL-18, and GSDMD-CT levels were assessed by ELISA. PTGS2 and ACSL4 expression were assessed by RT-PCR.Results: (2 × 6 Gy) group showed the highest ACSL4 expression followed by (3 × 4 Gy), then (4 × 2 Gy) and finally 6 Gy. (2 × 6 Gy) group resulted in the highest PTGS2 expression followed by (3 × 4 Gy), then 6 Gy, and finally (4 × 2 Gy). MDA significantly increased at (2 × 6 Gy), (3 × 4 Gy), and 6 Gy groups and insignificantly increased at (4 × 2 Gy) group. Iron significantly increased at (2 × 6 Gy), (3 × 4 Gy), and (4 × 2 Gy) groups and insignificantly at 6 Gy. Glutathione was significantly decreased at (2 × 6 Gy), (3 × 4 Gy), and (4 × 2 Gy) groups and insignificantly at 6 Gy. GSDMD-CT, IL-1β, and IL-18 levels significantly reduced in tumor tissues after exposure to IR at all doses.Conclusion: High dose per fraction regimens induce the expression of ferroptosis markers more than low dose per fraction regimen and single dose of IR. IR at all doses induces pyroptotic cell death.http://www.sciencedirect.com/science/article/pii/S2468294222000363FerroptosisPyroptosisFractionated radiation doseEhrlich solid tumor
spellingShingle Sanaa A El-Benhawy
Samar S Elblehi
Sabbah I Hammoury
Amira A Abo El-Soud
Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice
Cancer Treatment and Research Communications
Ferroptosis
Pyroptosis
Fractionated radiation dose
Ehrlich solid tumor
title Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice
title_full Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice
title_fullStr Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice
title_full_unstemmed Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice
title_short Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice
title_sort studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in ehrlich solid tumor bearing mice
topic Ferroptosis
Pyroptosis
Fractionated radiation dose
Ehrlich solid tumor
url http://www.sciencedirect.com/science/article/pii/S2468294222000363
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