Targeting the Canonical WNT/β-Catenin Pathway in Cancer Treatment Using Non-Steroidal Anti-Inflammatory Drugs
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Published on: June 17, 2014
Alexandre Vallée1, Yves Lecarpentier2, Jean-Noël Vallée3,4
1Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, Hotel-Dieu Hospital, AP-HP, Université Paris Descartes, 75004 Paris, France. alexandre.g.vallee@gmail.com.
Abstract:
Chronic inflammation and oxidative stress are common and co-substantial pathological processes accompanying and contributing to cancers. Numerous epidemiological studies have indicated that non-steroidal anti-inflammatory drugs (NSAIDs) could have a positive effect on both the prevention of cancer and tumor therapy. Numerous hypotheses have postulated that NSAIDs could slow tumor growth by acting on both chronic inflammation and oxidative stress. This review takes a closer look at these hypotheses. In the cancer process, one of the major signaling pathways involved is the WNT/β-catenin pathway, which appears to be upregulated. This pathway is closely associated with both chronic inflammation and oxidative stress in cancers. The administration of NSAIDs has been observed to help in the downregulation of the WNT/β-catenin pathway and thus in the control of tumor growth. NSAIDs act as PPARγ agonists. The WNT/β-catenin pathway and PPARγ act in opposing manners. PPARγ agonists can promote cell cycle arrest, cell differentiation, and apoptosis, and can reduce inflammation, oxidative stress, proliferation, invasion, and cell migration. In parallel, the dysregulation of circadian rhythms (CRs) contributes to cancer development through the upregulation of the canonical WNT/β-catenin pathway. By stimulating PPARγ expression, NSAIDs can control CRs through the regulation of many key circadian genes. The administration of NSAIDs in cancer treatment would thus appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/β-catenin pathway and PPARγ activity levels.
Insights
Non-steroidal anti-inflammatory drugs (NSAIDs) show promise in cancer prevention and therapy by targeting chronic inflammation and oxidative stress. They downregulate the WNT/β-catenin pathway and activate PPARγ, influencing cell growth and circadian rhythms.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Chronic inflammation and oxidative stress are key contributors to cancer development.
- The WNT/β-catenin signaling pathway is frequently upregulated in cancers and linked to inflammation and oxidative stress.
- Dysregulation of circadian rhythms also promotes cancer via WNT/β-catenin pathway activation.
Purpose of the Study:
- To review the hypotheses on how non-steroidal anti-inflammatory drugs (NSAIDs) impact cancer by modulating chronic inflammation and oxidative stress.
- To explore the role of NSAIDs in regulating the WNT/β-catenin pathway and PPARγ activity in cancer.
- To examine the connection between NSAIDs, circadian rhythms, and cancer progression.
Main Methods:
- Review of epidemiological studies and scientific literature on NSAIDs, cancer, inflammation, oxidative stress, WNT/β-catenin pathway, PPARγ, and circadian rhythms.
- Analysis of proposed mechanisms by which NSAIDs exert anti-cancer effects.
- Examination of the interplay between NSAIDs, signaling pathways, and cellular processes relevant to tumorigenesis.
Main Results:
- NSAIDs demonstrate potential in cancer prevention and therapy by mitigating chronic inflammation and oxidative stress.
- NSAIDs downregulate the WNT/β-catenin pathway, a key player in cancer progression.
- NSAIDs function as PPARγ agonists, promoting anti-cancer effects like cell cycle arrest, differentiation, and apoptosis, while reducing inflammation and proliferation.
- NSAIDs can influence circadian rhythms by regulating key circadian genes through PPARγ activation, potentially counteracting cancer-promoting CR dysregulation.
Conclusions:
- NSAIDs represent a promising therapeutic strategy for cancer treatment.
- Their efficacy stems from modulating the WNT/β-catenin pathway and PPARγ activity.
- NSAIDs' ability to regulate circadian rhythms adds another layer to their anti-cancer potential.
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