Lactam-Based HDAC Inhibitors for Anticancer Chemotherapy: Restoration of RUNX3 by Posttranslational Modification and Epigenetic Control
- Authors
- Cho, Misun; Choi, Eunhyun; Kim, Jae Hyun; Kim, Hwan; Kim, Hwan Mook; Lee, Jang Ik; Hwang, Ki-Chul; Kim, Hyun-Jung; Han, Gyoonhee
- Issue Date
- Mar-2014
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- drug discovery; histone deacetylase; inhibitors; lactam; runt-related transcription factor3
- Citation
- CHEMMEDCHEM, v.9, no.3, pp.649 - 656
- Journal Title
- CHEMMEDCHEM
- Volume
- 9
- Number
- 3
- Start Page
- 649
- End Page
- 656
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12813
- DOI
- 10.1002/cmdc.201300393
- ISSN
- 1860-7179
- Abstract
- Expression and stability of the tumor suppressor runt-related transcription factor3 (RUNX3) are regulated by histone deacetylase (HDAC). HDAC inhibition alters epigenetic and posttranslational stability of RUNX3, leading to tumor suppression. However, HDAC inhibitors can nonselectively alter global gene expression through chromatin remodeling. Thus, lactam-based HDAC inhibitors were screened to identify potent protein stabilizers that maintain RUNX3 stability by acetylation. RUNX activity and HDAC inhibition were determined for 111 lactam-based analogues through a cell-based RUNX activation and HDAC inhibition assay. 3-[1-(4-Bromobenzyl)-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-N-hydroxypropanamide (11-8) significantly increased RUNX3 acetylation and stability with relatively low RUNX3 mRNA expression and HDAC inhibitory activity. This compound showed significant antitumor effects, which were stronger than SAHA, in an MKN28 xenograft model. Thus, we propose a novel strategy, in which HDAC inhibitors serve as antitumor chemotherapeutic agents that selectively target epigenetic regulation and protein stability of RUNX3.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 약학대학 > 약학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12813)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.