Oroxylin A modulates mitochondrial function and apoptosis in human colon cancer cells by inducing mitochondrial translocation of wild-type p53
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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
Qinglong Guo, e-mail: email@example.com
Libin Wei, M.D, e-mail: firstname.lastname@example.org
Keywords: p53, translocation, oroxylin A, oxidative stress
Received: August 11, 2015 Accepted: January 09, 2016 Published: March 05, 2016
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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