CYP1-mediated metabolism of dietary flavonoids enhances their toxicity in breast cancer cells.

De Montfort University Open Research Archive

Show simple item record

dc.contributor.author Androutsopoulos, Vasilis
dc.contributor.author Ruparelia, K. C.
dc.contributor.author Arroo, R. R. J.
dc.contributor.author Tsatsakis, A.
dc.contributor.author Spandidos, D.
dc.date.accessioned 2010-03-15T12:37:54Z
dc.date.available 2010-03-15T12:37:54Z
dc.date.issued 2009
dc.identifier.citation Androutsopoulos, V., Ruparelia, K., Arroo, R., Tsatsakis, A. and Spandidos, D. (2009) CYP1-mediated metabolism of dietary flavonoids enhances their toxicity in breast cancer cells. Toxicology Letters, 189S, S113. en
dc.identifier.issn 0378-4274
dc.identifier.uri http://hdl.handle.net/2086/3558
dc.description.abstract Among the different mechanisms proposed to explain the toxic effects of dietary flavonoids towards cancerous cells, substratelike interactions with cytochrome P450 CYP1 enzymes have recently been explored. In the present study the metabolism of the flavonoids chrysin, baicalein, scutellarein, sinensetin and genkwanin by recombinant CYP1A1, CYP1B1 and CYP1A2 enzymes and their cytotoxicity in MDA-MB 468 human breast adenocarcinoma and MCF-10A normal breast cell lines, were investigated. Baicalein and 6-hydroxyluteolinwere the only conversion products of chrysin and scutellarein metabolism by CYP1 family enzymes respectively, while baicalein itself was not further metabolized. Sinensetin and genkwanin produced a greater number of metabolites and were shown to inhibit strongly in vitro proliferation of MDA-MB 468 cells at submicromolar and micromolar concentrations respectively, without essentially affecting the viability of MCF-10A cells. Cotreatment of the CYP1 family inhibitor acacetin reversed the toxicity noticed for these two flavones in MDA-MB 468 cells to 10_M. In contrast chrysin, baicalein and scutellarein inhibited proliferation of MDA-MB 468 cells to a lesser extent than sinensetin and genkwanin. The metabolism of genkwanin to apigenin and of chrysin to baicalein was favored by CYP1B1 and CYP1A1 respectively. Taken together the data suggests that CYP1 family enzymes contribute amajor part to the activation of dietary flavonoids to more toxic conversion products in breast cancer cells. en
dc.language.iso en en
dc.publisher Elsevier en
dc.subject Cancer en
dc.subject CYP1 en
dc.subject natural products en
dc.title CYP1-mediated metabolism of dietary flavonoids enhances their toxicity in breast cancer cells. en
dc.type Conference en
dc.identifier.doi http://dx.doi.org/10.1016/j.toxlet.2009.06.365
dc.researchgroup Chemistry for Health
dc.peerreviewed Yes en


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record