Radio-sensitizing potential of artesunate is mediated by targeting stemness and hypoxia markers in solid Ehrlich tumor implanted in mice

Morsi, Mohamed I.; El-benhawy, Sanaa A.; Elblehi, Samar S.; Almesrati, Osama O. A.; Arab, Amal RR

doi:10.21608/jcbr.2025.291546.1355

Radio-sensitizing potential of artesunate is mediated by targeting stemness and hypoxia markers in solid Ehrlich tumor implanted in mice

Document Type : Original Article

Authors

¹ Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

² Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

³ Pathology Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt

⁴ Diagnostic and Therapeutic Radiology Department, Faculty of Medical Technology, Misrata University, Libya

⁵ Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt

10.21608/jcbr.2025.291546.1355

Abstract

Background: Despite the development of various treatment strategies, cancer remains the main cause of death worldwide. Aim: The purpose of this study was to investigate the antitumor effects and radio sensitizing effect of artesunate in combination with ionizing radiation (IR) on the Ehrlich solid carcinoma (ESC). Material and Methods: This study included 8 groups, each included 8 ESC bearing mice. Group I: untreated ESC bearing mice as a control group. Group II: Mice were irradiated with a single dose of irradiation (IR, 6Gy). Group III: Mice treated with artesunate alone (50mg/kg/day). Group IV: Mice treated with the combination of a single dose of IR (6Gy) and artesunate (50mg/kg/day). Group V: Mice treated with artesunate alone (100 mg/kg/day). Group VI: Mice treated with the combination of single dose of IR (6Gy) and artesunate (100 mg/kg/day). Group VII: Mice treated with artesunate alone (200mg/kg/day). Group VIII: Mice treated with the combination of single dose of IR (6Gy) and artesunate (200mg/kg/day). The levels of CD44, ALDH1A1, VEGF and HIF-1-α in tissue homogenate were measured by ELISA. P53 was measured using Immunohistochemistry. Results: Tumor inhibition rate increased, and tumor volume decreased in ESC, indicating that artesunate possesses anti-proliferative effects. Artesunate induced apoptosis through increasing p53 expression. Combination of artesunate with IR significantly elevated tumor damage induced by ionizing radiation. Artesunate induces hypoxia and increases CSC makers in a dose dependent manner. Conclusion: High dose of artesunate could be used as a potent anti-tumor agent against ESC with radio-sensitizing effects through induction of apoptosis. Artesunate induces hypoxia which leads to increased CSCs markers.

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