UCP2-Related Mitochondrial Pathway Participates in Oroxylin A-Induced Apoptosis in Human Colon Cancer Cells

Qiao Chen; Wei Libin; Dai QinshengZhou YuxinYin QianLi ZhiyuXiao YuanmingGuo QinglongLu Na

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UCP2-Related Mitochondrial Pathway Participates in Oroxylin A-Induced Apoptosis in Human Colon Cancer Cells

机译：UCP2-Related线粒体途径参与木蝴蝶素A-Induced人类结肠癌细胞凋亡癌症细胞

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Oroxylin A is a flavonoid extracted from the root of Scutellaria baicalensis Georgi. Our previous research demonstrated that oroxylin A have various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion, and others. This paper explores the mechanism how oroxylin A induce apoptosis by regulating uncoupling protein 2 (UCP2) in human colon cancer cells. We found that the inhibition of UCP2 by UCP2 siRNA significantly increased the sensitivity of cells to drugs, reactive oxygen species (ROS) generation and the opening of mitochondrial permeability transition pore (MPTP) of CaCo-2 cells. We also found that UCP2 inhibition could lead to ROS-mediated MPTP activation. Furthermore, we demonstrated that oroxylin A triggered MPTP-dependent pro-apoptotic protein release from mitochondria to matrix and then induced apoptotic cascade by inhibiting UCP2. Intriguingly, the inhibition of UCP2 by oroxylin A was able to block Bcl-2 translocation to the mitochondria, keeping MPTP at open-state. In conclusion, we have demonstrated that UCP2 plays a key role in mitochondrial apoptotic pathway; UCP2s inhibition by oroxylin A triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells. J. Cell. Physiol. 230: 1054-1063, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company

机译：从根木蝴蝶素是一种黄酮类提取黄芩。研究表明,木蝴蝶素各种抗肿瘤的作用包括细胞凋亡、细胞周期阻滞、耐药逆转别人。木蝴蝶素诱导细胞凋亡的调节解偶联蛋白2 (UCP2)在人类结肠癌细胞。UCP2 siRNA显著增加了细胞对药物的敏感性,活性氧物种(ROS)生成和开放线粒体通透性转换孔注射(MPTP药物)CaCo-2细胞。抑制可能导致注射ROS-mediated MPTP药物激活。木蝴蝶素一个触发MPTP-dependent pro-apoptotic矩阵和蛋白质从线粒体释放然后由抑制诱导凋亡级联UCP2。木蝴蝶素能阻止bcl - 2易位注射到线粒体,保持MPTP药物处于公开状态。总之,我们已经表明,UCP2在线粒体凋亡起着关键的作用通路;注射的MPTP药物,并促进细胞凋亡CaCo-2细胞。2015. 公司

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来源
《Journal of Cellular Physiology》 |2015年第5期|1054-1063|共10页
作者
Qiao Chen; Wei Libin; Dai QinshengZhou YuxinYin QianLi ZhiyuXiao YuanmingGuo QinglongLu Na;
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作者单位

China Pharmaceut Univ, Jiangsu Key Lab Carcinogenesis & Intervent, State Key Lab Nat Med, Nanjing;

Nanjing Foreign Language Sch, Nanjing, Jiangsu, Peoples R China;

China Pharmaceut Univ, Dept Med Chem, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R;

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正文语种英语
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关键词
Caco-2 Cells; Breast Cancer Cell; Scutellaria baicalensis5,7-dihydroxy-6-methoxy-2-phenylchromen-4-oneUCP2 geneMitochondriaApoptosis;

机译：Caco-2细胞;乳腺癌细胞;黄芩baical;

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UCP2-Related Mitochondrial Pathway Participates in Oroxylin A-Induced Apoptosis in Human Colon Cancer Cells

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