ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2020; 11(14):4047-4058. doi:10.7150/jca.33045 This issue Cite
Research Paper
Xanthohumol suppresses glioblastoma via modulation of Hexokinase 2 -mediated glycolysis
1. Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China.
2. The Institute of Skull Base Surgery and Neuro-oncology at Hunan, 87 Xiangya Road, Changsha, Hunan, 410008, China.
Abstract
Deregulation of aerobic glycolysis is a common phenomenon in human cancers, including glioblastoma (GBM). In the present study, we demonstrated that the natural compound xanthohumol has a profound anti-tumor effect on GBM via direct inhibition of glycolysis. Xanthohumol suppressed cell proliferation and colony formation of GBM cells, and significantly impaired glucose metabolism via inhibiting Hexokinase 2 (HK2) expression. We demonstrated that down-regulation of c-Myc was required for xanthohumol-induced decrease of HK2. Xanthohumol destabilization of c-Myc, and promoted FBW7-mediated ubiquitination of c-Myc. Xanthohumol attenuated Akt activity and inhibited the activation of GSK3β, resulted in c-Myc degradation. Overexpression of Myr-Akt1 significantly rescued xanthohumol-mediated c-Myc inhibition and glycolysis suppression. Finally, the xanthohumol-mediated down-regulation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis promoted the destabilization of c-Myc. Finally, the animal results demonstrated that xanthohumol substantially inhibited tumor growth in vivo. Collectively, xanthohumol appears to be a promising new anti-tumor agent with the therapeutic potential for GBM.
Keywords: glioblastoma, xanthohumol, Hexokinases II, c-Myc, glycolysis
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