A novel bis-aryl urea compound inhibits tumor proliferation via cathepsin D-associated apoptosis. Issue 5 (June 2020)

• Record Type: Journal Article
• Authors: Wu, Jianping; Huang, Yao; Xie, Qian; Zhang, Junfeng; Zhan, Zhen
• Is Part Of: Anti-cancer drugs. Volume 31:Issue 5(2020)
• Publication Date: 2020-06
• Subjects: apoptosis -- bis-aryl urea compound -- cathepsin D -- N69B -- proliferation; Antineoplastic agents -- Periodicals; Cancer -- Chemotherapy -- Periodicals; Antineoplastic Agents -- therapeutic use -- Periodicals; Drug Therapy -- Periodicals; 616.994061
• DOI: 10.1097/CAD.0000000000000898
• Languages: English
• ISSNs: 0959-4973

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.