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.
Highlights
P53 is one of the most well-characterized proteins in cancer cell biology and is widely recognized as a tumor suppressor [1]
To confirm wt-p53 translocation to the www.impactjournals.com/oncotarget mitochondria in various cancer cells, we evaluated the subcellular distribution of p53 and reactive oxygen species (ROS) levels in wt-p53 cancer cells (e.g., HCT-116, MDA-MB-231, and HepG 2 cells), mut-p53 cancer cells (e.g., SW480, MCF-7), and normal cells (e.g., L02 cells) after tetradecanoylphorbol 13-acetate (TPA) treatment [14]
We previously demonstrated that oroxylin A can induce the mitochondrial apoptotic pathway [21,22,23,24]
Summary
P53 is one of the most well-characterized proteins in cancer cell biology and is widely recognized as a tumor suppressor [1]. The functions of p53 include regulation of substrate metabolism, DNA repair, autophagy, cell senescence, angiogenesis, and oxidative stress [2]. The Recql protein is essential for p53 mitochondrial translocation and recruits p53 to the mitochondria in response to stress [9, 10]. Localization of p53 to the mitochondria via a mitochondrial localization signal can induce mitochondrial DNA replication and contribute to changes in the mitochondrial physiological status [9]. Oroxylin A has been shown to have anticancer activities in vitro and in vivo through multiple mechanisms including cell cycle arrest, inhibition of metastasis, and apoptosis [11,12,13]. We provide evidence that oroxylin A facilitates mitochondrial translocation of p53 thereby inducing the mitochondrial apoptotic pathway
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
