Apigenin sensitizes radiotherapy of mouse subcutaneous glioma through attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolysis

We used radioresistant SU3-5R stem cells-inoculated subcutaneous glioma model to investigate the radiosensitization effect of apigenin. After treatment of glioma with apigenin 20 mg/kg for 12 days, irradiation 8 Gray twice or their combination, the tumor volume and weight were decreased, especially in the combination group. Apigenin inhibited the activities of glycolytic enzymes and expressions of nuclear factor kappa B (NF-kappa B) p65, hypoxia inducible factor-1 alpha (HIF-1 alpha), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues. After treatment of SU3-5R cells with apigenin 7.5 mu M, the fluorescence intensity of CD133 positive cells was decreased, the percentage of cells with comet tails was increased, and the expressions of lipopolysaccharide-induced NF-KB p65, HIF-1 alpha, GLUT-3 and PKM2 proteins were reduced. These results demonstrate that apigenin can sensitize the radiotherapy of glioma via the attenuations of cell stemness and DNA damage repair by inhibiting NF-KB/HIF-1 alpha-mediated glycolytic enzymes and protein expressions. (C) 2022 Elsevier Inc. All rights reserved.