Dataset Information

Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer.

ABSTRACT: The link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways. Cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism, is upregulated during both inflammation and cancer. COX-2 is induced by pro-inflammatory cytokines at the site of inflammation and enhanced COX-2-induced synthesis of prostaglandins stimulates cancer cell proliferation, promotes angiogenesis, inhibits apoptosis, and increases metastatic potential. As a result, COX-2 inhibitors are a subject of intense research interest toward potential clinical applications. Epidemiological studies highlight the potential benefits of diets rich in phytonutrients for cancer prevention. Plants contain numerous phytonutrient secondary metabolites shown to modulate COX-2. Studies have shown that these metabolites, some of which are used in traditional medicine, can reduce inflammation and carcinogenesis. This review describes the molecular mechanisms by which phytonutrients modulate inflammation, including studies of carotenoids, phenolic compounds, and fatty acids targeting various inflammation-related molecules and pathways associated with cancer. Examples of pathways include those of COX-2, mitogen-activated protein kinase kinase kinase, mitogen-activated protein kinase, pro-inflammatory cytokines, and transcription factors like nuclear factor kappa B. Such phytonutrient modulation of COX-2 and inflammation continue to be explored for applications in the prevention and treatment of cancer.

SUBMITTER: Desai SJ

PROVIDER: S-EPMC6309701 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer.

Desai Shreena J SJ Prickril Ben B Rasooly Avraham A

Nutrition and cancer 20180326 3

The link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways. Cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism, is upregulated during both inflammation and cancer. COX-2 is induced by pro-inflammatory cytokines at the site of inflammation and enhanced COX-2-induced synthesis of prostaglandins stimulates cancer cell proliferation, promotes angiogenesis, inhibits apoptosis, and increases metastatic potential. As a result, COX-2 inhibitor ...[more]

PMID: 29578814

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Project description:Gastric cancer accounts for the majority cancer-related deaths worldwide. Although various methods have considerably improved the screening, diagnosis, and treatment of gastric cancer, its incidence is still high in Asia, and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%. Therefore, more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer. Cyclooxygenase-2 (COX-2) is considered to be the key inducible enzyme in prostaglandins (PGs) synthesis, which is involved in multiple pathways in the inflammatory response. For example, inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway. In these processes, the production of an inflammatory microenvironment promotes the occurrence of gastric cancer. Epidemiological studies have also indicated that non-steroidal anti-inflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2. However, clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects, especially in the cardiovascular system. Given these side effects and low treatment efficacy, new therapeutic approaches and early screening strategies are urgently needed. Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis. However, the genetic variation analysis in these studies is incomplete and isolated, pointing out only a few single nucleotide polymorphisms (SNPs) and the risk of gastric cancer, and no comprehensive study covering the whole gene region has been carried out. In addition, copy number variation (CNV) is not mentioned. In this review, we summarize the SNPs in the whole COX-2 gene sequence, including exons, introns, and both the 5' and 3' untranslated regions. Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population. This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies, summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer, and discusses the future prospect of therapeutic intervention, which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.

Dataset Information

Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer.

Publications

Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer.

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