Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs.

Anthony M. Kyriakopoulos,Markus Nagl,Stella Baliou,Vasilleios Zoumpourlis

doi:10.1155/2017/9632018

Abstract

Clinical Relevance Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA) by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. Materials and Methods This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others) and library searches of books and journals. Results Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided.

Highlights

Increased risk is noticed by high doses of diclofenac and ibuprofen due to the increased myocardial infarction events recorded, whereas increased doses of naproxen have substantially smaller risk [55], suggesting differential inhibition of activity of COX-2
Acute myocardial infarction risk is potentiated in patients with coronary artery disease by high and low doses of diclofenac and rofecoxib and other Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), but not with naproxen even when administered in high doses [34]
Acetaminophen provides a unique example of cell-specific COX inhibition that may negatively affect the prostanoid synthesis in tumor cells by altering the levels of prostaglandin E2 (PGE2) [57, 58]

Summary

Introduction

Inflammation is driven by complex metabolic pathways, with arachidonic acid (AA) as one important molecule of origin. AA metabolism is fundamental for both promotion and inhibition of inflammatory processes. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) have been designed to decrease above all the classical symptoms of pain and tumefaction, but in the meantime it is known that they cause proinflammatory effects, too. Aspirin targets the COX-1 pathway, whereas the classical NSAIDs target mainly the COX-2 pathway by inhibiting prostaglandin E2 (PGE2) formation [4]. Aspirin acetylates the COX-2 isoenzyme but due to slight sequence variations this consumes less binding energy for arachidonic acid to become bound and be further metabolized [5]

Results

Discussion

Conclusion