2. Academic Validation
  3. Enhancing anti-cancer capacity: Novel class I/II HDAC inhibitors modulate EMT, cell cycle, and apoptosis pathways

Enhancing anti-cancer capacity: Novel class I/II HDAC inhibitors modulate EMT, cell cycle, and apoptosis pathways

  • Bioorg Med Chem. 2024 Jul 15:109:117792. doi: 10.1016/j.bmc.2024.117792.
Hsueh-Yun Lee 1,  Min-Jung Hsu 2,  Hao-Hsien Chang 3,  Wei-Chiao Chang 4,  Wan-Chen Huang 5,  Er-Chieh Cho 6
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; TMU Research Center for Drug Discovery, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 2 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 3 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 4 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 5 Single-Molecule Biology Core Lab, Institute of Cellular and Organismic Biology (ICOB), Academia Sinica, Taipei, Taiwan. Electronic address: [email protected].
  • 6 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taiwan; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
PMID: 38897139 DOI: 10.1016/j.bmc.2024.117792
Abstract

Cancer has been a leading cause of death over the last few decades in western countries as well as in Taiwan. However, traditional therapies are limited by the adverse effects of chemotherapy and radiotherapy, and tumor recurrence may occur. Therefore, it is critical to develop novel therapeutic drugs. In the field of HDAC Inhibitor development, apart from the hydroxamic acid moiety, 2-aminobenzamide also functions as a zinc-binding domain, which is shown in well-known HDAC inhibitors such as Entinostat and Chidamide. With recent successful experiences in synthesizing 1-(phenylsulfonyl)indole-based compounds, in this study, we further combined two features of the above chemical compounds and generated indolyl benzamides. Compounds were screened in different Cancer cell lines, and enzyme activity was examined to demonstrate their potential for anti-HDAC activity. Various biological functional assays evidenced that two of these compounds could suppress Cancer growth and migration capacity, through regulating epithelial-mesenchymal transition (EMT), cell cycle, and Apoptosis mechanisms. Data from 3D Cancer cells and the in vivo zebrafish model suggested the potential of these compounds in Cancer therapy in the future.

Keywords

Apoptosis; Cancer therapy; Cell cycle regulation; Epithelial-mesenchymal transition; Novel HDAC inhibitors.

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