1. Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress
- Author
-
Ying Huang, Wuping Yang, Huihong Zeng, Chuan Hu, Yaqiong Zhang, Nanhua Ding, Guangqin Fan, Lijian Shao, and Bohai Kuang
- Subjects
Droxinostat ,HT-29 cells ,Apoptosis ,ROS ,Cytology ,QH573-671 - Abstract
Abstract Upregulation of histone acetylation plays a critical role in the dysregulation of transcription. It alters the structure of chromatin, which leads to the onset of cancer. Histone deacetylase inhibitors may therefore be a promising way to limit cancer progression. In this study, we examined the effects of droxinostat on the growth of HT-29 colon cancer cells. Our results show that droxinostat effectively inhibited cell growth and colony-forming ability by inducing cellular apoptosis and ROS production in HT-29 cells. Notably, the apoptotic inhibitor Z-VAD-FMK significantly decreased the levels of cellular apoptosis and the antioxidant γ-tocotrienol (GT3) significantly decreased ROS production induced by droxinostat treatment. Z-VAD-FMK and GT3 also partially reversed the negative growth effects of droxinstat on HT-29 cells. GT3 treatment decreased cellular apoptosis and increased colony-forming ability upon droxinostat administration. Z-VAD-FMK treatment also partially decreased droxinostat-induced ROS production. Our findings suggest that the effects of droxinostat on colon cancer cells are mediated by the induction of oxidative stress and apoptotic cell death.
- Published
- 2018
- Full Text
- View/download PDF