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Xanthohumol suppresses glioblastoma via modulation of Hexokinase 2 -mediated glycolysis
- Source :
- Journal of Cancer
- Publication Year :
- 2020
- Publisher :
- Ivyspring International Publisher, 2020.
-
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.
- Subjects :
- 0301 basic medicine
biology
Chemistry
Cell growth
glioblastoma
glycolysis
Carbohydrate metabolism
xanthohumol
03 medical and health sciences
chemistry.chemical_compound
c-Myc
030104 developmental biology
0302 clinical medicine
Oncology
Ubiquitin
In vivo
Anaerobic glycolysis
030220 oncology & carcinogenesis
Xanthohumol
biology.protein
Cancer research
Glycolysis
Hexokinases II
Protein kinase B
Research Paper
Subjects
Details
- ISSN :
- 18379664
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of Cancer
- Accession number :
- edsair.doi.dedup.....a1b26e48c584e329fd009f6e832c4d90