CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells.

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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 2010-03-15T12:30:38Z
dc.date.available 2010-03-15T12:30:38Z
dc.date.issued 2009-08-08
dc.identifier.citation Androutsopoulos, V., Ruparelia, K., Arroo, R.R.J., Tsatsakis, A. and Spandidos, D. (2009) CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells. Toxicology, 264 (3) pp.162-170. en
dc.identifier.issn 0300-483X
dc.identifier.uri http://hdl.handle.net/2086/3557
dc.description.abstract Among the different mechanisms proposed to explain the cancer-protecting effect of dietary flavonoids, substrate-like 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, as well as their antiproliferative activity in MDA-MB-468 human breast adenocarcinoma and MCF-10A normal breast cell lines, were investigated. Baicalein and 6-hydroxyluteolin were the only conversion products of chrysin and scutellarein metabolism by CYP1 family enzymes, respectively, while baicalein itself was not metabolized further. 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 antiproliferative activity noticed for the two flavones in MDA-MB-468 cells to 13 and 14_M respectively. 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 enhance the antiproliferative activity of dietary flavonoids in breast cancer cells, through bioconversion to more active products. en
dc.language.iso en en
dc.publisher Elsevier en
dc.subject CYP1A1 en
dc.subject CYP1A2 en
dc.subject CYP1B1 en
dc.subject MDA-MB-468 cells en
dc.subject metabolism en
dc.subject flavonoids en
dc.title CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells. en
dc.type Article en
dc.identifier.doi http://dx.doi.org/10.1016/j.tox.2009.07.023
dc.researchgroup Chemistry for Health
dc.peerreviewed Yes en


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