Oncotarget

Research Papers:

Oroxylin A modulates mitochondrial function and apoptosis in human colon cancer cells by inducing mitochondrial translocation of wild-type p53

Chen Qiao _, Na Lu, Yuxin Zhou, Ting Ni, Yuanyuan Dai, Zhiyu Li, Qinglong Guo and Libin Wei

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Oncotarget. 2016; 7:17009-17020. https://doi.org/10.18632/oncotarget.7927

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Abstract

Chen Qiao1,*, Na Lu1,*, Yuxin Zhou1, Ting Ni1, Yuanyuan Dai1, Zhiyu Li2, Qinglong Guo1, Libin Wei1

1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People’s Republic of China

2Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of China

*These authors contributed equally to this work

Correspondence to:

Qinglong Guo, e-mail: anticancer_drug@163.com

Libin Wei, M.D, e-mail: wlbiws_1986@aliyun.com

Keywords: p53, translocation, oroxylin A, oxidative stress

Received: August 11, 2015     Accepted: January 09, 2016     Published: March 05, 2016

ABSTRACT

Oroxylin A is a flavonoid extracted from the root of Scutellaria baicalensis Georgi. We previously demonstrated that oroxylin A induced apoptosis in human colon cancer cells via the mitochondrial pathway. In the present study, we investigated the underlying mechanisms responsible for the mitochondrial apoptotic pathway triggered by oroxylin A. p53 regulates mitochondrial survival, mitochondrial DNA integrity, and protection from oxidative stress. We determined that oroxylin A induces p53 mitochondrial translocation and inhibits SOD2 activity. Additionally, our studies demonstrate that oroxylin A promotes the formation and mitochondrial translocation of the p53-Recql4 complex in HCT-116 cells. Finally, we showed that oroxylin A triggers cytosolic p53 activation, thereby promoting apoptosis. Mitochondrial translocation of p53 was also validated in vivo. Thus, oroxylin A induces mitochondrial translocation of p53 and leads to mitochondrial dysfunction in human colon cancer cells.


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