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

// Chen Qiao 1, * , Na Lu 1, * , Yuxin Zhou 1 , Ting Ni 1 , Yuanyuan Dai 1 , Zhiyu Li 2 , Qinglong Guo 1 , Libin Wei 1 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People’s Republic of China 2 Department 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.