State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, China Pharmaceutical University, Nanjing, PR China.
Cell Death Dis. 2013 Apr 18;4(4):e601. doi: 10.1038/cddis.2013.131.
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.
黄芩素 A 是中国传统药用植物黄芩的主要活性成分之一，已被报道为一种潜在的抗癌药物。我们证明，黄芩素 A 通过沉默信息调节因子 3（SIRT3）抑制人乳腺癌细胞系中的糖酵解和己糖激酶 II（HK II）与线粒体的结合。黄芩素 A 增加了线粒体中 SIRT3 的水平。然后，SIRT3 去乙酰化亲环蛋白 D，降低其肽基脯氨酰顺反式异构酶活性，并诱导其从腺嘌呤核苷酸转运蛋白中解离。最后，SIRT3 诱导的亲环蛋白 D 失活导致线粒体 HK II 的分离和糖酵解的抑制。这些结果对于乳腺癌中 SIRT3 调节的代谢重编程效应和对黄芩素 A 诱导的线粒体细胞毒性的敏感性具有重要意义。
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