Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway
- Resource Type
- Authors
- Amro Hamdoun; Victor Nizet; Terry Gaasterland; Tristan M. Carland; William H. Gerwick; Joseph P. Campanale; Lena Gerwick; Samantha J. Mascuch; N. Tessa Pierce; Mary E. Hensler; Joshua Olson; Paul D. Boudreau; Hyukjae Choi
- Source
- Journal of natural products, vol 81, iss 3
- Subject
- 0301 basic medicine
Aquatic Organisms
Alkylation
Response element
Anti-Inflammatory Agents
Pharmaceutical Science
Medical and Health Sciences
Antioxidants
Analytical Chemistry
Mice
Drug Discovery
Gene expression
Tumor
Kelch-Like ECH-Associated Protein 1
Chemistry
Biological Sciences
Cell biology
MCF-7 Cells
Molecular Medicine
Female
Signal transduction
medicine.symptom
Signal Transduction
Biotechnology
NF-E2-Related Factor 2
1.1 Normal biological development and functioning
Medicinal & Biomolecular Chemistry
Repressor
Article
Cell Line
03 medical and health sciences
Underpinning research
Cell Line, Tumor
Complementary and Integrative Health
medicine
Genetics
Animals
Humans
Nutrition
Pharmacology
Inflammation
Biological Products
Organic Chemistry
KEAP1
In vitro
Cytosol
030104 developmental biology
RAW 264.7 Cells
Complementary and alternative medicine
Mechanism of action
Cytoprotection
Chemical Sciences
- Language
The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-L-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keapl. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.