Unlocking Aspirin's Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1
- PMID: 27998883
- PMCID: PMC5292092
- DOI: 10.1158/1940-6207.CAPR-16-0241
Unlocking Aspirin's Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1
Abstract
The mechanism by which aspirin consumption is linked to significant reductions in the incidence of multiple forms of cancer and metastatic spread to distant tissues, resulting in increased cancer patient survival is not well understood. In this study, using colon cancer as an example, we provide both in vitro (cell culture) and in vivo (chemically induced mouse model of colon cancer) evidence that this profound antineoplastic action may be associated with aspirin's ability to irreversibly inhibit COX-1-mediated platelet activation, thereby blocking platelet-cancer cell interactions, which promote cancer cell number and invasive potential. This process may be driven by platelet-induced epithelial-mesenchymal transition (EMT), as assessed using confocal microscopy, based upon changes in cell morphology, growth characteristics and fibronectin expression, and biochemical/molecular analysis by measuring changes in the expression of the EMT markers; vimentin, β-catenin, and SNAIL. We also provide evidence that a novel, gastrointestinal-safe phosphatidylcholine (PC)-associated aspirin, PL2200 Aspirin, possesses the same or more pronounced actions versus unmodified aspirin with regard to antiplatelet effects (in vitro: reducing platelet activation as determined by measuring the release of thromboxane and VEGF in culture medium; in vivo: inhibiting platelet number/activation and extravasation into tumor tissue) and chemoprevention (in vitro: inhibiting colonic cell growth and invasive activity; in vivo: inhibiting colonic dysplasia, inflammation, and tumor mass). These results suggest that aspirin's chemopreventive effects may be due, in part, to the drug blocking the proneoplastic action of platelets, and the potential use of Aspirin-PC/PL2200 as an effective and safer chemopreventive agent for colorectal cancer and possibly other cancers. Cancer Prev Res; 10(2); 142-52. ©2016 AACR.
©2016 American Association for Cancer Research.
Conflict of interest statement
of Potential Conflicts of Interest: L. Lichtenberger is a co-founder and shareholder in PLx Pharma Inc which is developing PC-NSAIDs for commercial use.
Figures
![Figure 1](https://webcf.waybackmachine.org/web/20220408220641im_/https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5292092/bin/nihms838620f1.gif)
![Figure 2](https://webcf.waybackmachine.org/web/20220408220641im_/https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5292092/bin/nihms838620f2.gif)
![Figure 3](https://webcf.waybackmachine.org/web/20220408220641im_/https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5292092/bin/nihms838620f3.gif)
![Figure 4](https://webcf.waybackmachine.org/web/20220408220641im_/https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5292092/bin/nihms838620f4.gif)
![Figure 5](https://webcf.waybackmachine.org/web/20220408220641im_/https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5292092/bin/nihms838620f5.gif)
![Figure 6](https://webcf.waybackmachine.org/web/20220408220641im_/https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5292092/bin/nihms838620f6.gif)
Similar articles
-
Are Platelets the Primary Target of Aspirin's Remarkable Anticancer Activity?Cancer Res. 2019 Aug 1;79(15):3820-3823. doi: 10.1158/0008-5472.CAN-19-0762. Epub 2019 Jul 12. Cancer Res. 2019. PMID: 31300475 Free PMC article. Review.
-
Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.Cancer Metastasis Rev. 2017 Jun;36(2):289-303. doi: 10.1007/s10555-017-9675-z. Cancer Metastasis Rev. 2017. PMID: 28762014 Free PMC article. Review.
-
Pharmacogenomics of platelet responsiveness to aspirin.Pharmacogenomics. 2007 Oct;8(10):1413-25. doi: 10.2217/14622416.8.10.1413. Pharmacogenomics. 2007. PMID: 17979514 Review.
-
Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin.J Thromb Haemost. 2007 Mar;5(3):490-6. doi: 10.1111/j.1538-7836.2007.02387.x. J Thromb Haemost. 2007. PMID: 17319904 Clinical Trial.
-
Mechanisms of the antitumoural effects of aspirin in the gastrointestinal tract.Best Pract Res Clin Gastroenterol. 2012 Aug;26(4):e1-e13. doi: 10.1016/j.bpg.2012.10.001. Best Pract Res Clin Gastroenterol. 2012. PMID: 23199511 Review.
Cited by 20 articles
-
Transcriptome-wide In Vitro Effects of Aspirin on Patient-derived Normal Colon Organoids.Cancer Prev Res (Phila). 2021 Dec;14(12):1089-1100. doi: 10.1158/1940-6207.CAPR-21-0041. Epub 2021 Aug 13. Cancer Prev Res (Phila). 2021. PMID: 34389629
-
Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues.Front Oncol. 2021 Jul 12;11:665534. doi: 10.3389/fonc.2021.665534. eCollection 2021. Front Oncol. 2021. PMID: 34322381 Free PMC article. Review.
-
Mechanisms of Colorectal Cancer Prevention by Aspirin-A Literature Review and Perspective on the Role of COX-Dependent and -Independent Pathways.Int J Mol Sci. 2020 Nov 27;21(23):9018. doi: 10.3390/ijms21239018. Int J Mol Sci. 2020. PMID: 33260951 Free PMC article. Review.
-
Application of Anti-Inflammatory Agents in Prostate Cancer.J Clin Med. 2020 Aug 18;9(8):2680. doi: 10.3390/jcm9082680. J Clin Med. 2020. PMID: 32824865 Free PMC article. Review.
-
What is the potential use of platelet-rich-plasma (PRP) in cancer treatment? A mini review.Heliyon. 2020 Mar 28;6(3):e03660. doi: 10.1016/j.heliyon.2020.e03660. eCollection 2020 Mar. Heliyon. 2020. PMID: 32258495 Free PMC article. Review.
MeSH terms
Substances
Grant support
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials