The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Bladder Cancer.
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Date (from‐to) : 2016/04 -2019/03
Author : TAOKA RIKIYA; Stephen Safe; Kamat Ashish
CF3DODA-Me is a new compound derived synthetically from licorice. In this study, we have investigated the anticancer effects of CF3DODA-Me, and determined its effects on Specificity protein (Sp) transcription factors and reactive oxygen species (ROS) activity in bladder cancer cells. In bladder cancer cells, CF3DODA-Me induced ROS, and inhibited cell viability, survival, and the expression of Sp and Sp-regulated proteins (VEGF, VEGFR2, Bcl-2, Survivin). These anticancer effects were clearly attenuated by co-treatment with antioxidant GSH. Silencing of Sp reduced Sp-regulated proteins and induced apoptosis. In bladder cancer stem cells, CF3DODA-Me downregulated Sp and Sp-regulated proteins, and inhibited sphere formation. In vivo setting, CF3DODA-Me also reduced the expression of Sp, increased amount of active caspase-3 positive cells, and inhibited tumor growth as compared to the control. These results demonstrated a novel ROS-dependent mechanism of anticancer activity for CF3DODA-Me.