title: 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: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: L
authors: L
authors: Wei
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: Y
authors: Y
authors: Zhou
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: C
authors: C
authors: Qiao
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: T
authors: T
authors: Ni
authors: JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: Z
authors: Z
authors: Li
authors: JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: Q
authors: Q
authors: You
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: Q
authors: Q
authors: Guo
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors: N
authors: N
authors: Lu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D056566:Sirtuin 3 / Q000235:genetics* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099156:Superoxide Dismutase 2
chemical_list: D005419:Flavonoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D056566:Sirtuin 3; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; C466093:SIRT3 protein, human