Oxidative Stress Influences Exosome Biogenesis by Inducing Cellular Senescence in Uterine Adenocarcinoma Ishikawa Cells
Nasimi F.S. Alimohammadzadeh B. Mehdizadeh A. Al-Koofee D.A.F. Tamadon A. Mahdipour M. Rahbarghazi R.
December 2025Shiraz University of Medical Sciences
Iranian Journal of Medical Sciences
2025#50Issue 12832 - 842 pp.
Background: The progression of life and cellular senescence can alter the physiological activity of every cell type. Here, the possible effect of oxidative stress on exosome (Exo) biogenesis was studied in endometrial adenocarcinoma Ishikawa cells. Methods: This in vitro study was conducted from 2022 to 2023 at the Stem Cell Research Center affiliated with Tabriz University of Medical Sciences. Cells were treated with 20 μM hydrogen peroxide (H2 O2) for 4 days, and physicochemical properties of Exos were analyzed using dynamic light scattering (DLS), scanning electron microscope (SEM), and western blotting. The expression of genes such as ALIX, CD63, TSG101, Rab27a, and Rab27b, along with aging factor senescence-associated β-galactosidase (SA-β-gal), was studied using real-time PCR analysis. The fatty acid profile was determined in isolated Exos using gas chromatography. We also measured the exosomal content of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Results: The expression of SA-β-gal confirmed the successful induction of aging in Ishikawa cells after 4 days (P=0.0286). DLS analysis indicated a slight increase and decrease in mean Exo size and zeta potential, respectively, in H2 O2-treated Exos compared to the control group. Proteomic analysis revealed the lack of changes in exosomal levels of CD63 and CD81 tetraspanins in both groups (P=0.001). Real-time PCR analysis indicated the upregulation of ALIX and TSG101, while the expression of CD63 and Rab27b was reduced in H2 O2-treated cells compared to the control group (P=0.0015 and P=0.0129). No statistically significant changes were found in exosomal levels of SOD, GPx, and MDA before and after treatment with the H2 O2 (P=0.857, P=0.421, and P=0.3739). Data indicated an increase in exosomal polyunsaturated fatty acids and monounsaturated fatty acids in H2 O2-treated cells compared to the control cells. Conclusion: Oxidative stress can influence Exo biogenesis and paracrine activity in endometrial tumor cells via the induction of cellular senescence.
Biogenesis , Cellular senescence , Extracellular vesicles , Paracrine communication , Uterine neoplasms
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Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Clinical Laboratory Science, Faculty of Pharmacy, University of Kufa, Kufa, Najaf, 54003, Iraq
Department of Natural Sciences, West-Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Stem Cell Research Center
Hematology and Oncology Research Center
Department of Clinical Laboratory Science
Department of Natural Sciences
Department of Reproductive Biology
Department of Applied Cell Sciences
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