期刊
CELL DEATH & DISEASE
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2015.86
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资金
- National Science & Technology Major Project [2012ZX09103101-050, 2012ZX09304-001]
- National Natural Science Foundation of China [91029744, 81373448]
- Natural Science Foundation of Jiangsu Province, China [BK2010432]
- Program for New Century Excellent Talents in University [NCET-12-0973]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZJQ201302]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT1193]
- Graduate Innovation Fund of SIMCERE PHARMACEUTICAL GROUP, China [CX11B-006XS]
- Doctoral Talents Cultivation Plan of China Pharmaceutical University, China [2011 II BPY07]
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 1 alpha (HIF1 alpha), 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 HIF1 alpha stabilization via SIRT3 activation, providing preclinical information for the cancer therapies of SIRT3 stimulation.
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