Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1α destabilization.

Abstract	Alterations of cellular metabolism play a central role in the development and progression of cancer. Oroxylin A, an active flavonoid of a Chinese traditional medicinal plant, was previously shown to modulate glycolysis in cancer cells. However, the mechanism by which oroxylin A regulates glycolysis is still not well defined. Here, we show that oroxylin A inhibits glycolysis in breast cancer cells via the Sirtuin 3 (SIRT3)-mediated destabilization of hypoxia-inducible factor 1α (HIF1α), which controls glycolytic gene expression. Oroxylin A promotes superoxide dismutase (SOD2) gene expression through SIRT3-regulated DNA-binding activity of FOXO3a and increases the activity of SOD2 by promoting SIRT3-mediated deacetylation. In vivo, oroxylin A inhibits the growth of transplanted human breast tumors associated with glycolytic suppression. These data indicate that oroxylin A inhibits glycolysis-dependent proliferation of breast cancer cells, through the suppression of HIF1α stabilization via SIRT3 activation, providing preclinical information for the cancer therapies of SIRT3 stimulation.
Authors	L Wei, Y Zhou, C Qiao, T Ni, Z Li, Q You, Q Guo, N Lu
Journal	Cell death & disease (Cell Death Dis) Vol. 6 Pg. e1714 (Apr 09 2015) ISSN: 2041-4889 [Electronic] England
PMID	25855962 (Publication Type: Journal Article)
Chemical References	Flavonoids Hypoxia-Inducible Factor 1, alpha Subunit 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one Superoxide Dismutase superoxide dismutase 2 SIRT3 protein, human Sirtuin 3
Topics	Animals Breast Neoplasms (drug therapy, genetics, metabolism, pathology) Cell Line, Tumor Cell Proliferation (drug effects) Female Flavonoids (pharmacology) Glycolysis (drug effects) Humans Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism) Mice Mice, Inbred BALB C Mice, Nude Sirtuin 3 (genetics, metabolism) Superoxide Dismutase (genetics, metabolism) Transfection Xenograft Model Antitumor Assays

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