Study explains how NSAIDs halt cancer growth

The study was led by researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with scientists at Columbia University Medical Center.

In cases of chronic inflammation, certain signaling pathways that modulate the inflammatory processes become “stuck” in an activated state. This leads to the release of molecules that enhance carcinogenesis and tumor progression.

These anticancer effects have been attributed, in large part, to the painkiller’s potential to induce cell death, which appears to stem from the drugs’ inhibition of the COX enzymes, the primary mechanism by which non-steroidal anti-inflammatory drugs (NSAID) guard against pain.

“However, COX inhibition did not appear to be the only anticancer pathway being targeted by the compounds. We, therefore, undertook a comprehensive review of NSAIDs in order to decipher the precise molecular mechanisms that were at work,” said Towia Libermann, director of the BIDMC Genomics Center.

The researchers examined more than 20,000 genes to identify potential mechanisms for cell death induction. MDA-7/IL-24 was the gene that stood out.

Following their identification of this cytokine, the investigators used an interfering RNA approach to block MDA-7/IL-24 gene expression in cancer cells, thereby demonstrating the necessity of NSAID-mediated induction of the gene to destroy cancer cells. They also used a mouse model of prostate cancer to demonstrate that when MDA-7/IL-24 was blocked, the anticancer effects of the NSAIDs were diminished.

“The level of MDA-7/IL-24 gene expression in cancer patients may emerge as a new biomarker for monitoring patients’ responses to certain therapies, and may help determine whether drugs such as NSAIDs are hitting their intended targets,” noted Towia Libermann.