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Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress.


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 ?-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.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC6064062 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress.

Huang Ying Y   Yang Wuping W   Zeng Huihong H   Hu Chuan C   Zhang Yaqiong Y   Ding Nanhua N   Fan Guangqin G   Shao Lijian L   Kuang Bohai B  

Cellular & molecular biology letters 20180728


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 produ  ...[more]

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