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.
Highlights
Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract: it is the third most commonly diagnosed cancer and the fourth most common cause of cancer death worldwide [1, 2]
Droxinostat inhibited the growth of human colon cancer cells To estimate the effects of droxinostat on the growth of colon cancer cells, 400 HT-29 cells were seeded onto a 96-well plate and treated with different concentrations of droxinostat
Our results indicate that Histone deacetylase inhibitors (HDACIs) can inhibit the growth of colon cancer cells
Summary
Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract: it is the third most commonly diagnosed cancer and the fourth most common cause of cancer death worldwide [1, 2]. Chemotherapy regimens based on 5-fluorouracil (5-FU) remain the standard treatment for CRC in both adjuvant and advanced disease settings and improves overall survival [3]. Response rates to 5-FU therapy are between 10 and 20% in the metastatic setting [4]. Resistance to chemotherapy is still a major reason for treatment failure in colon cancer [5]. Novel and efficacious therapeutic agents and strategies are urgently needed for the treatment of colon cancer. Histone deacetylase inhibitors (HDACIs) were recently identified as a promising new target in cancer therapy. Multiple studies have demonstrated that HDACIs can arrest cell growth, block angiogenesis, and induce differentiation and apoptosis in tumor cells [6]. Histones are typically catalyzed by two enzyme families: histone acetyltransferases
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