Ibuprofen May Help Kill Colorectal Cancer Cells

Inhibition of cyclooxygenases make ibuprofen kill colorectal cancer cells, as per the study published in Oncotarget.

One example is its ability to inhibit the alternative splicing event generating RAC1B, which is overexpressed in a specific subset of BRAF-mutated colorectal tumors and sustains cell survival.

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‘New study shed light on the biochemical mechanisms behind ibuprofen's action on alternative spliced RAC1B and may support its use in personalized approaches to colorectal cancer.’
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Here the authors describe the mechanism by which ibuprofen prevents RAC1B alternative splicing in a BRAF mutant CRC cell line: it leads to decreased translocation of SRPK1 and SRSF1 to the nucleus and is regulated by a WNK1/GSK3β/SRPK1 protein kinase complex.

Surprisingly, they demonstrate that ibuprofen does not inhibit the activity of any of the involved kinases but rather promotes disassembly of this regulatory complex, exposing GSK3β serine 9 to inhibitory phosphorylation, namely by AKT, which results in nuclear exclusion of SRPK1 and SRSF1 hypophosphorylation.

Dr. Peter Jordan from The National Health Institute Dr. Ricardo Jorge as well as The University of Lisbon said, "Cancer is the second leading cause of death globally and one major risk factor for tumor development is chronic inflammation."

A long term use of nonsteroidal anti-inflammatory drugs, like ibuprofen and aspirin, which are among the most commonly prescribed medications worldwide, was shown to provide chemoprevention against various types of cancer.

Ibuprofen, like most NSAIDs, inhibits both COX isoforms so that side-effects such as intestinal bleeding or cardiovascular disease can occur, questioning the long-term use of NSAIDs for cancer chemoprevention.

Interestingly, some NSAIDs were reported to inhibit tumor growth by targeting other cellular processes and elucidation of the underlying biochemical processes could lead to the development of safer and more efficacious drugs for cancer chemoprevention or adjuvant therapy.

In the case of ibuprofen, numerous studies have shown that its cancer chemopreventive properties are much more complex and involve multiple COX-independent effects.

The Jordan Research Team concluded in their Oncotarget Research Output, "our data suggest that ibuprofen treatment interferes with a signal transduction pathway involved in the regulation of alternative spliced RAC1B.

One other report on prostate cancer cells receiving combined treatment of ibuprofen and epigallocatechin-3-gallate, reported changes in alternative splicing, in particular promoting the shorter and proapoptotic BCL-X (S) or MCL-1(S) variants."

Source-Eurekalert