Selective Activation of an Apoptotic Retinoid Precursor in Macrophage Cell Lines
Year: 1998
Type: article
Abstract: Advances in the understanding of the retinoid signaling mechanism has allowed the discovery of highly selective retinoids that activate only one specific receptor class, subtype, or signaling pathway. These novel compounds lack certain of the common retinoid toxicities and therefore suggest promising new approaches for therapeutic applications. We describe here a new compound, 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid methyl ester (MX84), that is selectively activated in macrophages, leading to killing of only macrophage monocyte type cells in vitro. We provide evidence that MX84 is an inactive precursor that is converted into an active apoptosis-inducing retinoid in macrophages. The macrophage activity is also secreted, and our data suggest that the secreted activity is a phospholipase D type activity. Our observation may lead to the development of molecules that are highly macrophage-selective apoptosis inducers in vivo and that could represent important novel therapeutics against diseases caused by excessive macrophage activity.
Source: Journal of Biological Chemistry
Authors: Serge V. Yarovoi, Xian-Ping Lu, Nathalie Picard, Deepa Rungta, Darryl Rideout, Magnus Pfahl
Institution: Sidney Kimmel Cancer Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funder: National Cancer Institute
OpenAlex ID: W2075324767