Oroxylin A Induces Dissociation of Hexokinase II from the Mitochondria and Inhibits Glycolysis by SIRT3-mediated Deacetylation of Cyclophilin D in Breast Carcinoma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2013 Apr 20

PMID 23598413

Citations 61

Authors

L Wei

Y Zhou

Q Dai

C Qiao

L Zhao

H Hui

N Lu

Q-L Guo

Affiliations

Soon will be listed here.

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.

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