Looking at NSAIDs from a historical perspective and their current status in drug repurposing for cancer treatment and prevention

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed drug classes with wide therapeutic applications over the centuries. Starting from the use of salicylate-containing willow leaves to the recent rise and fall of highly selective cyclooxygenase-2 (COX-2) inhibitors and the latest dual-acting anti-inflammatory molecules, they have displayed a rapid and ongoing evolution. Despite the enormous advances in the last twenty years, investigators are still in search of the design and development of more potent and safer therapy against inflammatory conditions. This challenge has been increasingly attractive as the emergence of inflammation as a common seed and unifying mechanism for most chronic diseases. Indeed, this fact put the NSAIDs in the spotlight for repurposing against inflammation-related disorders. This review attempts to present a historical perspective on the evolution of NSAIDs, regarding their COX-dependent/independent mode of actions, structural and mechanism-based classifications, and adverse effects. Additionally, a systematic review of previous studies was carried out to show the current situation in drug repurposing, particularly in cancers associated with the GI tract such as gastric and colorectal carcinoma. In the case of non-GI-related cancers, preclinical studies elucidating the effects and modes of action were collected and summarized.

Activity-dependent COX-2 proteolysis generates a catalytically inactive fragment that affects aerobic respiration and proliferation

“…In terms of its expression, COX-2 is an immediate-early gene that is rapidly and massively upregulated to meet the high demand for PGs during inflammation, and elevated COX-2 levels are hallmarks of chronic inflammation and many types of malignancies 27 . Whereas the majority of the high-volume literature concerning COX-2 focuses on its transcriptional regulation 1 and the pharmacological means to inhibit its enzymatic activity 28 , very little is known about pathways that clear COX-2 from the cell. This question is of particular importance given the rapid inactivation of COX-2 by its catalysis products.…”

Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin

“…Currently, the discovery of chemotherapeutic agents has been directed toward drug repurposing, focusing on several classes of anti-inflammatory drugs [ 40 ], especially the non-steroidal anti-inflammatory drugs (NSAIDs) [ 41 ]. Crude extracts from various parts of C. siamea were reported to exhibit in vivo anti-inflammatory activity [ 38 , 42 ].…”

Charting the Knowledge and Patterns of Non-Steroidal Anti-Inflammatory Drugs Usage in Hail Population, Saudi Arabia: Insights into the Adverse Effect Profile

“…Moreover, earlier studies demonstrated the potential advantages of NSAIDs in reducing the likelihood of delirium and mortality [ 8 ]. Despite the significant progress made over the past two decades, researchers continue to seek methods to design and develop more effective and safer therapies for treating inflammatory conditions [ 9 ]. This quest has become particularly compelling due to recognizing inflammation as a shared underlying factor and a unifying mechanism in most chronic diseases [ 9 ].…”