Aspirin-triggered proresolving mediators stimulate resolution in cancer.

Document Type

Article

Publication Date

3-26-2019

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Keywords

eicosanoids; inflammation; metabolomics; metastasis; resolvins

Abstract

Inflammation in the tumor microenvironment is a strong promoter of tumor growth. Substantial epidemiologic evidence suggests that aspirin, which suppresses inflammation, reduces the risk of cancer. The mechanism by which aspirin inhibits cancer has remained unclear, and toxicity has limited its clinical use. Aspirin not only blocks the biosynthesis of prostaglandins, but also stimulates the endogenous production of anti-inflammatory and proresolving mediators termed aspirin-triggered specialized proresolving mediators (AT-SPMs), such as aspirin-triggered resolvins (AT-RvDs) and lipoxins (AT-LXs). Using genetic and pharmacologic manipulation of a proresolving receptor, we demonstrate that AT-RvDs mediate the antitumor activity of aspirin. Moreover, treatment of mice with AT-RvDs (e.g., AT-RvD1 and AT-RvD3) or AT-LXA

Clinical Institute

Cancer

Department

Institute for Systems Biology

Link to Full Text

PSJH Full Text

Share

COinS