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Cyclooxygenase-2 inhibitors in tumorigenesis (Part II)
1Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo, Japan. taketo@mol.f.u-tokyo.ac.jp
Abstract:
The rate-limiting step in arachidonate metabolism is mediated by enzymes known as cyclooxygenases (COXs). These enzymes catalyze the biosynthesis of prostaglandin H2, the precursor of molecules such as prostaglandins, prostacyclin, and thromboxanes. The COX enzyme family consists of the classical COX-1 enzyme, which is constitutively expressed in many tissues, and a second isozyme, i.e., COX-2, which is induced by various stimuli, such as mitogens and cytokines, and is involved in many inflammatory reactions. Because nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, these drugs also cause unwanted side effects, exemplified by gastrointestinal bleeding. Accumulating evidence indicates that NSAIDs can reduce the incidence of colorectal cancers in human and experimental animals and can reduce the number and size of polyps in patients with familial adenomatous polyposis. This Part II (of a two-part review) focuses on the growing clinical and experimental evidence that NSAIDS and COX-2 inhibitors can influence the risk of colon (and possibly of other) cancers.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors show promise in reducing colorectal cancer risk. Further research explores their influence on various cancers.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Arachidonate metabolism is regulated by cyclooxygenases (COXs), producing prostaglandins, prostacyclin, and thromboxanes.
- COX-1 is constitutively expressed, while COX-2 is induced during inflammation.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, leading to side effects like gastrointestinal bleeding.
Purpose of the Study:
- To review clinical and experimental evidence on NSAIDs and COX-2 inhibitors' role in cancer risk.
- To focus on their influence on colon cancer and potentially other cancer types.
Main Methods:
- Review of existing clinical studies.
- Analysis of experimental animal data.
- Examination of evidence regarding NSAIDs and COX-2 inhibitors' effects on cancer incidence and progression.
Main Results:
- NSAIDs have demonstrated a reduction in colorectal cancer incidence in humans and animals.
- NSAIDs can decrease polyp number and size in patients with familial adenomatous polyposis.
- Growing evidence suggests NSAIDs and COX-2 inhibitors impact colon cancer risk.
Conclusions:
- NSAIDs and selective COX-2 inhibitors represent a potential strategy for colon cancer prevention.
- Further investigation is warranted to fully understand their role in various cancers and optimize therapeutic strategies.