NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase
Acute inflammation or resolved inflammation is an adaptive host defense mechanism and is self-limiting, which returns the body to a state of homeostasis. However, unresolved, uncontrolled, or chronic inflammation may lead to various maladies, including cancer. Important evidence that links inflammat...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/3/1432 |
| _version_ | 1797487473559863296 |
|---|---|
| author | Oluwafunke R. Kolawole Khosrow Kashfi |
| author_facet | Oluwafunke R. Kolawole Khosrow Kashfi |
| author_sort | Oluwafunke R. Kolawole |
| collection | DOAJ |
| description | Acute inflammation or resolved inflammation is an adaptive host defense mechanism and is self-limiting, which returns the body to a state of homeostasis. However, unresolved, uncontrolled, or chronic inflammation may lead to various maladies, including cancer. Important evidence that links inflammation and cancer is that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the risk and mortality from many cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug developmental work focusing on cyclooxygenase (COX) and its products. The increased prostaglandin E2 levels and the overexpression of COX-2 in the colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, NSAIDs do not require the presence of COX-2 to prevent cancer. In this review, we highlight the effects of NSAIDs and selective COX-2 inhibitors (COXIBs) on targets beyond COX-2 that have shown to be important against many cancers. Finally, we hone in on specialized pro-resolving mediators (SPMs) that are biosynthesized locally and, in a time, -dependent manner to promote the resolution of inflammation and subsequent tissue healing. Different classes of SPMs are reviewed, highlighting aspirin’s potential in triggering the production of these resolution-promoting mediators (resolvins, lipoxins, protectins, and maresins), which show promise in inhibiting cancer growth and metastasis. |
| first_indexed | 2024-03-09T23:48:12Z |
| format | Article |
| id | doaj.art-d80c22720ab248679d045c4e4b49e927 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:48:12Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d80c22720ab248679d045c4e4b49e9272023-11-23T16:40:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233143210.3390/ijms23031432NSAIDs and Cancer Resolution: New Paradigms beyond CyclooxygenaseOluwafunke R. Kolawole0Khosrow Kashfi1Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USADepartment of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USAAcute inflammation or resolved inflammation is an adaptive host defense mechanism and is self-limiting, which returns the body to a state of homeostasis. However, unresolved, uncontrolled, or chronic inflammation may lead to various maladies, including cancer. Important evidence that links inflammation and cancer is that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the risk and mortality from many cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug developmental work focusing on cyclooxygenase (COX) and its products. The increased prostaglandin E2 levels and the overexpression of COX-2 in the colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, NSAIDs do not require the presence of COX-2 to prevent cancer. In this review, we highlight the effects of NSAIDs and selective COX-2 inhibitors (COXIBs) on targets beyond COX-2 that have shown to be important against many cancers. Finally, we hone in on specialized pro-resolving mediators (SPMs) that are biosynthesized locally and, in a time, -dependent manner to promote the resolution of inflammation and subsequent tissue healing. Different classes of SPMs are reviewed, highlighting aspirin’s potential in triggering the production of these resolution-promoting mediators (resolvins, lipoxins, protectins, and maresins), which show promise in inhibiting cancer growth and metastasis.https://www.mdpi.com/1422-0067/23/3/1432NSAIDsaspirincyclooxygenasenon-Cox targetsresolutioncancer |
| spellingShingle | Oluwafunke R. Kolawole Khosrow Kashfi NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase International Journal of Molecular Sciences NSAIDs aspirin cyclooxygenase non-Cox targets resolution cancer |
| title | NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase |
| title_full | NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase |
| title_fullStr | NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase |
| title_full_unstemmed | NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase |
| title_short | NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase |
| title_sort | nsaids and cancer resolution new paradigms beyond cyclooxygenase |
| topic | NSAIDs aspirin cyclooxygenase non-Cox targets resolution cancer |
| url | https://www.mdpi.com/1422-0067/23/3/1432 |
| work_keys_str_mv | AT oluwafunkerkolawole nsaidsandcancerresolutionnewparadigmsbeyondcyclooxygenase AT khosrowkashfi nsaidsandcancerresolutionnewparadigmsbeyondcyclooxygenase |