Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors. Issue 3 (16th March 2017)

• Record Type: Journal Article
• Authors: Smith, Christina E.; Soti, Subada; Jones, Torey A.; Nakagawa, Akihisa; Xue, Ding; Yin, Hang
• Is Part Of: Cell chemical biology. Volume 24:Issue 3(2017)
• Page Start: 281
• Page End: 292
• Publication Date: 2017-03-16
• Subjects: NSAIDs -- caspase -- pharmacology -- anti-inflammation; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2017.02.003
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity in both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design. Graphical Abstract: Highlights: Caspases are identified as a novel target for a subset of NSAIDs Inhibition occurs at physiologically relevant concentrations in vitro and in vivo New molecular insight expands anti-inflammatory drug mechanism Abstract : Smith et al. report the identification and characterization of caspases as general NSAID pharmacological targets. Inhibition occurs at physiologically relevant concentrations both in vitro and in vivo, and expands the NSAID anti-inflammatory mechanism.