A novel bis-aryl urea compound inhibits tumor proliferation via cathepsin D-associated apoptosis: Derivatives of bis-aryl urea have been widely investigated for their various biological activities, such as antiviral, anti-inflammatory and antiproliferative. We evaluated a new chemical entity consisting of bis-aryl urea moiety, N69B, for its anticancer activities and explored their underlying molecular mechanism. The compound inhibited proliferation of multiple types of murine and human cancer cells in vitro, and reduced tumor growth in mouse 4T1 breast tumor model in vivo. Protein microarray analysis revealed and western blot confirmed that the compound significantly increased protein levels of cathepsins, especially cathepsin D, a lysosomal aspartyl protease known to have various pathophysiological functions. Further studies showed that the compound induced tumor cell apoptosis through the Bid/Bax/Cytochrome C/caspase 9/caspase 3 pathway, in which cathepsin D appeared to be a main mediator. Unlike kinase inhibition commonly seen with many other anticancer bis-aryl urea derivatives, this unique mechanism of N69B may suggest potential of the compound as a novel anticancer drug.
Received 17 October 2019 Revised form accepted 16 December 2019
Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.anti-cancerdrugs.com.
Correspondence to Zhen Zhan, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Box 21, 138 Xianlin Road, Nanjing 210032, Jiangsu, China, E-mail: 290114@njucm.edu.cn
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CC-BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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Τρίτη 7 Ιανουαρίου 2020
A novel bis-aryl urea compound inhibits tumor proliferation via cathepsin D-associated apoptosis
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