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Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents - implications for cancer treatment and chemoprevention

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Abstract

Background

Epigenetic processes and miRNAs have been recognized as new targets for anticancer drug design. However, old multi-target drugs such as aspirin may also target epigenetic processes.

Aim

This review aims to provide an overview of our current knowledge on the modulation of epigenetic processes by aspirin and other non steroidal anti-inflammatory agents (NSAIDs) and their implications for cancer treatment and chemoprevention.

Synthesis

In vitro and in vivo studies, as well as primary patient data, suggest that aspirin and other NSAIDs reverse tumour suppressor gene hypermethylation in cancer tissues. It must be emphasized that, at this point in time, patient data are limited and DNA hypermethylation reversal has been investigated, but not tumour suppressor gene activation. In addition, evidence from experimental and patient data suggests that aspirin and NSAIDs may also reverse global DNA hypomethylation. At the histone level, both induction and inhibition of deacetylases by aspirin have been reported. Also, direct acetylation of histones by aspirin has been reported, while the natural salicylate anacardic acid has been found to inhibit histone acetyltransferase p300 both in vitro and in vivo, and to regulate gene expression through modulation of histone acetylation. Salicylates and other NSAIDs may also down-regulate miRNAs with oncogene-like functions or up-regulate miRNAs with tumour suppressor-like functions. Up till now, clinical trials have been aimed at investigating the effect of salicylates and NSAIDs on a limited number of miRNAs.

Conclusion

So, although the existing evidence is still limited, evidence is accumulating that epigenetic targets may represent nodal targets for the anti-proliferative actions of salicylates and NSAIDs. This, in turn, may have implications for cancer chemoprevention and treatment. Undoubtedly, this notion requires further investigation, but if proved correct, it could lead to the design of less toxic agents that target epigenetic processes as part of existing or novel multi-targeted treatment modalities.

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  1. Medical Laboratories, Faculty of Health and Caring Professions Technological Educational Institute of Athens, Eleutheriou Benizelou 106 Kallithea 17676, Athens, Greece

    Eugenia Yiannakopoulou

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Yiannakopoulou, E. Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents - implications for cancer treatment and chemoprevention. Cell Oncol. 37, 167–178 (2014). https://doi.org/10.1007/s13402-014-0175-7

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