Quercetin and Nf-kB / AP-1 induced apoptosis (WP2435)

Homo sapiens

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.

Authors

Chris Boye , Alex Pico , Nuno , Zahra Roudbari , Linda Rieswijk , Marianthi Kalafati , Denise Slenter , Andika Tan , Finterly Hu , Eric Weitz , and Egon Willighagen

Activity

last edited

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

regulatory pathway apoptotic cell death pathway

Participants

Label Type Compact URI Comment
Prostaglandin G2 Metabolite hmdb:HMDB0003235
Quercetin Metabolite hmdb:HMDB0005794
Prostaglandin H2 Metabolite hmdb:HMDB0001381
Arachidonic acid Metabolite hmdb:HMDB0001043
Prostaglandin I2 Metabolite hmdb:HMDB0001335
Thromboxane A2 Metabolite hmdb:HMDB0001452
Prostaglandin F2a Metabolite hmdb:HMDB0001139
Prostaglandin D2 Metabolite hmdb:HMDB0001403
Prostaglandin E2 Metabolite hmdb:HMDB0001220
COX1 GeneProduct ncbigene:4512
IKBKB GeneProduct ensembl:ENSG00000104365
NFKB1 GeneProduct ensembl:ENSG00000109320
MAFK GeneProduct ncbigene:7975
Phospholipase A2 GeneProduct eccode:3.1.1.4
MAFG GeneProduct ncbigene:4097
ACOX2 GeneProduct ensembl:ENSG00000168306
NFKBIA GeneProduct ensembl:ENSG00000100906
FOS GeneProduct ensembl:ENSG00000170345
NOS1 GeneProduct ensembl:ENSG00000089250
VEGFA GeneProduct ensembl:ENSG00000112715
JUN GeneProduct ensembl:ENSG00000177606
MMP1 GeneProduct ensembl:ENSG00000196611
CYP2A6 GeneProduct ensembl:ENSG00000255974 one of several possible phase 1 enzymes
NFE2L2 GeneProduct ensembl:ENSG00000116044
KEAP1 GeneProduct ensembl:ENSG00000079999
COX2 GeneProduct ncbigene:5743
NFKBIA Protein ensembl:ENSG00000100906

References

  1. The role of phytochemicals in inhibition of cancer and inflammation: New directions and perspectives. Issa AY, Volate SR, Wargovich MJ. Journal of Food Composition and Analysis [Internet]. 2006 Aug;19(5):405–19. Available from: http://dx.doi.org/10.1016/j.jfca.2006.02.009 DOI Scholia
  2. Prostaglandins and leukotrienes: advances in eicosanoid biology. Funk CD. Science. 2001 Nov 30;294(5548):1871–5. PubMed Europe PMC Scholia
  3. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Tanigawa S, Fujii M, Hou DX. Free Radic Biol Med. 2007 Jun 1;42(11):1690–703. PubMed Europe PMC Scholia
  4. Prostaglandins and inflammation. Ricciotti E, FitzGerald GA. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986–1000. PubMed Europe PMC Scholia