Version 1
: Received: 26 April 2024 / Approved: 28 April 2024 / Online: 29 April 2024 (03:43:14 CEST)
How to cite:
Roggero, A.; Annunciato, I.; Nicodemo, I.; Costa, C. R.; Fernandes, G. A.; Junior, A. B.; Rafael, M.; Oliveira, M. A. D.; Sousa, S. F.; Toyama, M. H. NSAIDs, from COX Inhibitors to PAF-AH Modulators: Exploring Unconventional Enzymatic Targets for Antitumor Therapy. Preprints2024, 2024041851. https://doi.org/10.20944/preprints202404.1851.v1
Roggero, A.; Annunciato, I.; Nicodemo, I.; Costa, C. R.; Fernandes, G. A.; Junior, A. B.; Rafael, M.; Oliveira, M. A. D.; Sousa, S. F.; Toyama, M. H. NSAIDs, from COX Inhibitors to PAF-AH Modulators: Exploring Unconventional Enzymatic Targets for Antitumor Therapy. Preprints 2024, 2024041851. https://doi.org/10.20944/preprints202404.1851.v1
Roggero, A.; Annunciato, I.; Nicodemo, I.; Costa, C. R.; Fernandes, G. A.; Junior, A. B.; Rafael, M.; Oliveira, M. A. D.; Sousa, S. F.; Toyama, M. H. NSAIDs, from COX Inhibitors to PAF-AH Modulators: Exploring Unconventional Enzymatic Targets for Antitumor Therapy. Preprints2024, 2024041851. https://doi.org/10.20944/preprints202404.1851.v1
APA Style
Roggero, A., Annunciato, I., Nicodemo, I., Costa, C. R., Fernandes, G. A., Junior, A. B., Rafael, M., Oliveira, M. A. D., Sousa, S. F., & Toyama, M. H. (2024). NSAIDs, from COX Inhibitors to PAF-AH Modulators: Exploring Unconventional Enzymatic Targets for Antitumor Therapy. Preprints. https://doi.org/10.20944/preprints202404.1851.v1
Chicago/Turabian Style
Roggero, A., Sergio F. Sousa and Marcos H. Toyama. 2024 "NSAIDs, from COX Inhibitors to PAF-AH Modulators: Exploring Unconventional Enzymatic Targets for Antitumor Therapy" Preprints. https://doi.org/10.20944/preprints202404.1851.v1
Abstract
A novel interaction between the enzyme platelet-activating factor acetyl hydrolase (PAF-AH) and certain non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac, celecoxib, diclofenac and nimesulide, has been uncovered by this in-silico research. PAF-AH is known for its critical role in maintaining the fluidity and functionality of cell membranes by hydrolysing phospholipids and removing oxidized fatty acids. Since tumour microenvironments are largely marked by inflammation and oxidative stress, the discovery that these non-steroidal anti-inflammatory drugs can bind to the active pocket of PAF-AH. Suggests that they may be able to modulate its activity and thereby influence its role in cancer pathogenesis. Such modulation could lead to significant anti-tumour effects, including the reduction of inflammation, the inhibition of angiogenesis and the suppression of metastasis, particularly in cancers of the breast, colon, prostate, and lung. However, in certain con-texts, this interaction may cause the opposite effect, leading to cancer development. Therefore, this study is a gateway for the development of therapeutic strategies based on PAF-AH modulation and highlights the importance of the tumour microenvironment in the assessment of potential effects of NSAIDs. Furthermore, this finding may guide the selection of NSAIDs for the anti-inflammatory treatment of cancer patients, ruling out in-discriminate use of drugs that may promote neoplastic progression. This may also indicate the potential for repositioning specific NSAIDs within cancer treatment, thereby contributing to more precise and personalized therapeutic approaches.
Keywords
platelet-activating factor acetyl hydrolase; non-steroidal anti-inflammatory drugs; cancer
Subject
Medicine and Pharmacology, Complementary and Alternative Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
