Quercetin and Nf-kB / AP-1 induced apoptosis (Homo sapiens)
From WikiPathways
Description
Quercetin is a flavonoid that is widely distributed in nature. In this pathway, its dual nature is depicted. On the one hand, it is capable of exerting anti-oxidant and anti-inflammatory effects by inhibiting the PLA2-induced conversion of cell membrane phospholipids to arachidonic acid, reducing the downstream synthesis of pro-inflammatory prostaglandins; furthermore, inhibition of NF-kB and AP-1 transcription factor activation also contribute to these effects.
On the other hand, quercetin itself may - paraxodically - generate ROS, as well as facilitate the activation of NFE2L2, which results in the production of CYP2A6. This isotype of CYP450 was found to be involved in the formation of carcinogenic metabolites. Both of these effects culminate in DNA damage. It has been observed, however, that these pro-oxidant effects are dominant at higher concentrations, whereas anti-oxidant effects are dominant at lower concentrations. Based on this, it has been suggested that quercetin may have a scavenging effect.
Quality Tags
Ontology Terms
Bibliography
- Funk CD; ''Prostaglandins and leukotrienes: advances in eicosanoid biology.''; Science, 2001 PubMed Europe PMC Scholia
- Tanigawa S, Fujii M, Hou DX; ''Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin.''; Free Radic Biol Med, 2007 PubMed Europe PMC Scholia
- Ricciotti E, FitzGerald GA; ''Prostaglandins and inflammation.''; Arterioscler Thromb Vasc Biol, 2011 PubMed Europe PMC Scholia
- Ala Y. Issaa, Suresh R. Volatea, Michael J. Wargovich; ''The role of phytochemicals in inhibition of cancer and inflammation: New directions and perspectives''; Journal of Food Composition and Analysis, 2006 DOI Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ACOX2 | GeneProduct | ENSG00000168306 (Ensembl) | |
Angiogenesis | Pathway | WP1539 (WikiPathways) | |
Arachidonic acid | Metabolite | HMDB0001043 (HMDB) | |
COX1 | GeneProduct | 4512 (Entrez Gene) | |
COX2 | GeneProduct | 5743 (Entrez Gene) | |
CYP2A6 | GeneProduct | ENSG00000255974 (Ensembl) | one of several possible phase 1 enzymes |
Carcinogenesis | Pathway | ||
Carcinogenic metabolite | Metabolite | ||
DNA damage | Pathway | ||
FOS | GeneProduct | ENSG00000170345 (Ensembl) | |
IKBKB | GeneProduct | ENSG00000104365 (Ensembl) | |
JUN | GeneProduct | ENSG00000177606 (Ensembl) | |
KEAP1 | GeneProduct | ENSG00000079999 (Ensembl) | |
MAFG | GeneProduct | 4097 (Entrez Gene) | |
MAFK | GeneProduct | 7975 (Entrez Gene) | |
MMP1 | GeneProduct | ENSG00000196611 (Ensembl) | |
Metastasis | Pathway | ||
NFE2L2 | GeneProduct | ENSG00000116044 (Ensembl) | |
NFKB1 | GeneProduct | ENSG00000109320 (Ensembl) | |
NFKBIA | Protein | ENSG00000100906 (Ensembl) | |
NOS1 | GeneProduct | ENSG00000089250 (Ensembl) | |
Phase 2 enzyme | Protein | ||
Phospholipase A2 | GeneProduct | 3.1.1.4 (Enzyme Nomenclature) | |
Prostaglandin D2 | Metabolite | HMDB0001403 (HMDB) | |
Prostaglandin E2 | Metabolite | HMDB0001220 (HMDB) | |
Prostaglandin F2a | Metabolite | HMDB0001139 (HMDB) | |
Prostaglandin G2 | Metabolite | HMDB0003235 (HMDB) | |
Prostaglandin H2 | Metabolite | HMDB0001381 (HMDB) | |
Prostaglandin I2 | Metabolite | HMDB0001335 (HMDB) | |
Quercetin | Metabolite | HMDB0005794 (HMDB) | |
Thromboxane A2 | Metabolite | HMDB0001452 (HMDB) | |
VEGFA | GeneProduct | ENSG00000112715 (Ensembl) |
Annotated Interactions
No annotated interactions