Isfahan University of Medical Sciences Journal of Isfahan Medical School 1027-7595 42 799 2025 02 19 Induction of Apoptosis in HepG2 Cancer Cells by Mesenchymal Stem Cell-Derived Exosomes via Reactive Oxygen Species Production Induction of Apoptosis in HepG2 Cancer Cells by Mesenchymal Stem Cell-Derived Exosomes via Reactive Oxygen Species Production 1206 1214 31372 10.48305/jims.v42.i799.1206 FA Sahar Saki MSc, Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 0009-0006-7525-6627 Mahdi Hatami Assistant Professor, Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 0000-0002-7810-5780 Fatemeh Ghaffari MSc, Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 0009-0003-1027-0493 Azam Khedri Assistant Professor, Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 0000-0001-9623-1054 Samaneh Salehipour Bavarsad Assistant Professor, Cellular and Molecular Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 0000-0001-7336-2166 Journal Article 2024 09 16 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Current treatment methods, such as chemotherapy and radiation therapy, can cause damage to patients' organs and occasionally lead to death. Etoposide (ETO), a widely used chemotherapeutic agent, has similar issues. Exosomes derived from mesenchymal stem cells represent a novel approach that may reduce side effects by targeted delivery of bioactive molecules to cancer cells. Methods: HepG2 cancer cells were first cultured in a DMEM medium containing 10% fetal bovine serum (FBS) until reaching appropriate confluence. Then, the HepG2 cells were treated with 25 and 50 µM concentrations of exosomes for 24 hours. Subsequently, the expression levels of BAX and BCL-2 genes, ROS levels, and the apoptosis rate were measured. Findings: Treatment of HepG2 cells with exosomes derived from mesenchymal stem cells led to an increase in BAX gene expression and a decrease in BCL-2 gene expression. Additionally, the levels of reactive oxygen species (ROS) and apoptosis rates were significantly higher compared to the control group, indicating a positive effect of exosomes in inducing programmed cell death. Conclusion: Exosomes derived from MSCs were able to induce apoptosis in HepG2 cancer cells through the production of ROS. These findings suggest that exosomes can be utilized as a promising novel therapeutic approach in cancer treatment and offer strategies for developing safer and more effective cancer therapies. Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Current treatment methods, such as chemotherapy and radiation therapy, can cause damage to patients' organs and occasionally lead to death. Etoposide (ETO), a widely used chemotherapeutic agent, has similar issues. Exosomes derived from mesenchymal stem cells represent a novel approach that may reduce side effects by targeted delivery of bioactive molecules to cancer cells. Methods: HepG2 cancer cells were first cultured in a DMEM medium containing 10% fetal bovine serum (FBS) until reaching appropriate confluence. Then, the HepG2 cells were treated with 25 and 50 µM concentrations of exosomes for 24 hours. Subsequently, the expression levels of BAX and BCL-2 genes, ROS levels, and the apoptosis rate were measured. Findings: Treatment of HepG2 cells with exosomes derived from mesenchymal stem cells led to an increase in BAX gene expression and a decrease in BCL-2 gene expression. Additionally, the levels of reactive oxygen species (ROS) and apoptosis rates were significantly higher compared to the control group, indicating a positive effect of exosomes in inducing programmed cell death. Conclusion: Exosomes derived from MSCs were able to induce apoptosis in HepG2 cancer cells through the production of ROS. These findings suggest that exosomes can be utilized as a promising novel therapeutic approach in cancer treatment and offer strategies for developing safer and more effective cancer therapies.

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