A New Twist to Ibuprofen: Alternative Action in Alternative Splicing

Abstract

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) and is a widely used medication. One indication of NSAID use is long-term chemoprevention to decrease the risk of developing various types of cancer, in particular colorectal cancer. The molecular mechanism behind the antitumour properties of NSAID has been largely attributed to inhibition of the enzyme cyclooxygenase. In this review article, the authors highlight that additional mechanisms of NSAID, especially ibuprofen, action exist that are related to cell signalling and the modulation of gene expression, including alternative splicing. For example, the authors describe how ibuprofen inhibits expression of the tumour-related splicing variant RAC1b, which is overexpressed in a specific subset of colorectal tumours. The mechanism involves changes in the phosphorylation of splicing factors that regulate this alternative splicing event. According to recent studies, ibuprofen interferes with signal transmission via protein kinases, a process which is frequently altered in cancer cells.