A novel HDAC1/2 inhibitor suppresses colorectal cancer through apoptosis induction and cell cycle regulation

Hsueh Yun Lee, Di Wei Tang, Chi Yuan Liu, Er Chieh Cho

研究成果: 雜誌貢獻文章同行評審

摘要

Colorectal cancer (CRC) is one of the leading causes of death around the world, and synthetic chemicals targeting specific proteins or various molecular pathways for tumor suppression, such as histone deacetylases (HADC) inhibitors, are under intensively studied. The target of HDAC involves in regulating critical cellular mechanisms and underpins the progression of anticancer therapy. However, little is known about the antitumor mechanisms of class I specific HDAC inhibitors in CRC. We structurally designed and synthesized benzamide-based compounds, examined their anticancer activity in several solid tumors, and identified compound 9 with high potential. Results from the in vitro enzyme and cell-based studies demonstrated that compound 9 as a selective HDAC1/2 inhibitor that possessed short-term and long-term suppression capacities against colorectal cancer cells. Investigation of molecular regulatory mechanisms of 9 in colorectal cancer cells by biological functional assays evidenced that treatment of compound 9 could activate apoptosis, induce cell cycle arrest, facilitate DNA damage process, and suppress cancer migration. A non-cancerous cell line and the in vivo zebrafish model were applied for safety evaluation. In summary, our results demonstrate that compound 9 is a promising lead drug worth further investigation for development of future cancer therapeutic agents.

原文英語
文章編號109778
期刊Chemico-Biological Interactions
352
DOIs
出版狀態已發佈 - 1月 25 2022

ASJC Scopus subject areas

  • 毒理學

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