Back to Search
Start Over
Flavonoid GL-V9 induces apoptosis and inhibits glycolysis of breast cancer via disrupting GSK-3β-modulated mitochondrial binding of HKII.
- Source :
-
Free Radical Biology & Medicine . Jan2020, Vol. 146, p119-129. 11p. - Publication Year :
- 2020
-
Abstract
- Energy metabolism plays important roles in the growth and survival of cancer cells. Here, we find a newly synthesized flavonoid named GL-V9, which inhibits glycolysis and induces apoptosis of human breast cancer cell lines, and investigate the underlying mechanism. Results show that hexokinase II (HKII) plays important roles in the anticancer effects of GL-V9. GL-V9 not only downregulates the expression of HKII in MDA-MB-231 and MCF-7 cells, but also induces dissociation of HKII from voltage-dependent anion channel (VDAC) in mitochondria, resulting in glycolytic inhibition and mitochondrial-mediated apoptosis. The dissociation of mitochondrial HKII is attributed to GSK-3β-induced phosphorylation of mitochondrial VDAC. Our in vivo experiments also show that GL-V9 significantly inhibits the growth of human breast cancer due to activation of GSK-3β and inactivation of AKT. Thus, GL-V9 induces cytotoxicity in breast cancer cells via disrupting the mitochondrial binding of HKII. Our works demonstrate the significance of metabolic regulators in cancer growth and offer a fresh insight into the molecular basis for the development of GL-V9 as a candidate for breast carcinoma treatment. Image 1 • GL-V9 inhibits aerobic glycolysis and induces apoptosis of breast cancer cells. • GL-V9 induces dissociation of HKII from VDAC in mitochondria. • GL-V9 promotes GSK-3β-induced phosphorylation of mitochondrial VDAC. • GL-V9 inhibits AKT and activitates GSK-3β both in vitro and in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 146
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 140957977
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2019.10.413