Molecular targets of aspirin and cancer prevention.

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Alfonso L, Ai G, Spitale RC, Bhat GJ

Molecular targets of aspirin and cancer prevention.

Br J Cancer. 2014 Jul 8;111(1):61-7. doi: 10.1038/bjc.2014.271. Epub 2014 May 29.

PubMed ID

24874482 [ View in PubMed

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Abstract

Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug.

DrugBank Data that Cites this Article

Drugs

Acetylsalicylic acid

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	Caspase-1	Protein	Humans	Unknown	Inhibitor Downregulator	Details
Acetylsalicylic acid	Caspase-3	Protein	Humans	Unknown	Inhibitor Downregulator	Details
Acetylsalicylic acid	Extracellular signal-regulated kinase (ERK) (Protein Group)	Protein group	Humans	Unknown	Not Available	Details
Acetylsalicylic acid	Inhibitor of nuclear factor kappa-B kinase subunit beta	Protein	Humans	Unknown	Not Available	Details