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Apigenin increases radiosensitivity of glioma stem cells by attenuating HIF-1α-mediated glycolysis

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Abstract

Apigenin, a natural flavonoid compound present in a variety of edible plants and health foods, has an anti-tumor effect and inhibits hypoxia inducible factor-lα (HIF-1α) expression in hypertrophic cardiac tissues. However, whether or not apigenin has a radiosensitization effect on glioma stem cells (GSCs) is unknown. Our present study aimed to investigate the effect of apigenin and its possible mechanisms. The human GSCs SU3 and its radioresistance line SU3-5R were treated with apigenin, radiation, or their combination, and the cell proliferation, migration, colony formation, and intracellular lactic acid and glycolytic related protein expressions were determined. Additionally, a cell model with hypoxia-induced HIF-1α expression was used and treated with apigenin. The current results displayed that the combination of apigenin and radiation could synergically reduce the viability, colony formation, and migration of the both GSCs. Moreover, this combination could also decrease the radiation-induced increments of glycolytic production lactic acid in the both GSCs and related protein expressions, including HIF-1α, glucose transporter (GLUT)-1/3, nuclear factor kappa B (NF-κB) p65, and pyruvate kinase isozyme type M2 (PKM2). Further study confirmed that after treatment of hypoxia-cultured SU3 or SU3-5R cells with apigenin, the expression levels of HIF-1α, GLUT-1/3, NF-κB p65, and PKM2 proteins were reduced. These results demonstrated that apigenin could increase the radiosensitivity of GSCs and its radiosensitization mechanisms were attributable to the attenuation of glycolysis, which might result from the inhibition of HIF-1α expression and subsequent reductions of GLUT-1/3, NF-κB, and PKM2 expressions.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Science & Technology Project of Suzhou City for Medical Health (KJXW2020039).

Funding

This study was supported by the Science & Technology Project of Suzhou City for Medical Health (KJXW2020039), China.

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Author notes

  1. Ying Zhao and Hui Huang have contributed equally to this work.

Authors and Affiliations

  1. College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China

    Ying Zhao, Hui Huang, Chang-Hao Jia, Ke Fan & Mei-Lin Xie

  2. Department of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China

    Tao Xie

  3. Department of Pharmacy, The Affiliated Children’s Hospital of Soochow University, Suzhou, Jiangsu, China

    Ying Zhao & Zeng-Yan Zhu

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  1. Ying Zhao
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  3. Chang-Hao Jia
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  4. Ke Fan
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  5. Tao Xie
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Contributions

YZ and HH performed the cell culture, pharmacodynamic study, and Western blot analysis. YZ wrote the first draft of the manuscript. HH and C-HJ collected and analyzed the experimental data. KF performed the measurements of biochemistry indexes. TX, Z-YZ, and M-LX designed the study and reviewed the manuscript. All authors approved the final manuscript.

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Correspondence to Tao Xie, Zeng-Yan Zhu or Mei-Lin Xie.

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Zhao, Y., Huang, H., Jia, CH. et al. Apigenin increases radiosensitivity of glioma stem cells by attenuating HIF-1α-mediated glycolysis. Med Oncol 38, 131 (2021). https://doi.org/10.1007/s12032-021-01586-8

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