title: Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma.
abstract: Oroxylin A is a major active component of the Chinese traditional medicinal plant Scutellaria baicalensis Georgi, which has been reported as a potential anticancer drug. We demonstrated that, Oroxylin A inhibited the glycolysis and the binding of hexokinase II (HK II) with mitochondria in human breast carcinoma cell lines, which was dependent on sirtuin-3 (SIRT3). The level of SIRT3 in mitochondria was increased by Oroxylin A. Then SIRT3 deacetylated cyclophilin D, diminished its peptidyl-prolyl cis-trans isomerase activity and induced its dissociation from the adenine nucleotide translocator. Finally, SIRT3-induced inactivation of cyclophilin D resulted in the detachment of mitochondrial HK II and the inhibition of glycolysis. These results have important implications for the metabolism reprogramming effect and the susceptibility to Oroxylin A-induced mitochondrial cytotoxicity through the regulation of SIRT3 in breast carcinoma.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, China Pharmaceutical University, Nanjing, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: Q
authors.initials: Q
authors.lastname: Dai
authors.forename: C
authors.initials: C
authors.lastname: Qiao
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Hui
authors.forename: N
authors.initials: N
authors.lastname: Lu
authors.forename: Q-L
authors.initials: QL
authors.lastname: Guo
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D018517:Plant Roots / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D031363:Scutellaria / Q000737:chemistry; D056566:Sirtuin 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D005419:Flavonoids; D034741:RNA, Small Interfering; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D006593:Hexokinase; D056566:Sirtuin 3; D021983:Cyclophilins