Browsing by Author "Androutsopoulos, Vasilis"

Now showing 1 - 14 of 14
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    Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation.
    (Spandidos, 2009) Androutsopoulos, Vasilis; Mahale, S.; Arroo, R. R. J.; Potter, Gerard A.
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    Anticancer effects of the metabolic products of the resveratrol analogue, DMU-212: Structural requirements for potency.
    (Elsevier, 2011) Androutsopoulos, Vasilis; Ruparelia, K. C.; Papakyriakou, A.; Filippakis, H.; Tsatsakis, A. M.; Spandidos, D. A.
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    Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism
    (BioMed Central, 2008) Androutsopoulos, Vasilis; Arroo, R. R. J.; Hall, J. F.; Surichan, Somchaiya; Potter, Gerard A.
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    Bioactivation of the citrus flavonoid nobiletin by CYP1 enzymes in MCF7 breast adenocarcinoma cells
    (Elsevier, 2012) Surichan, Somchaiya; Androutsopoulos, Vasilis; Sifakis, S.; Koutala, E.; Tsatsakis, A.; Arroo, R. R. J.; Boarder, M. R.
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    Bioactivation of the phytoestrogen diosmetin by CYP1 cytochromes P450
    (Elsevier, 2009) Androutsopoulos, Vasilis; Wilsher, N.; Arroo, R. R. J.; Potter, Gerard A.
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    CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells.
    (Elsevier, 2009-08-08) Androutsopoulos, Vasilis; Ruparelia, K. C.; Arroo, R. R. J.; Tsatsakis, A.; Spandidos, D.
    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.
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    CYP1-mediated metabolism of dietary flavonoids enhances their toxicity in breast cancer cells.
    (Elsevier, 2009) Androutsopoulos, Vasilis; Ruparelia, K. C.; Arroo, R. R. J.; Tsatsakis, A.; Spandidos, D.
    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.
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    CYP1-mediated toxicity of dietary flavonoids in MDA-MB-468 breast cancer cells.
    (Elsevier, 2009) Androutsopoulos, Vasilis; Ruparelia, K. C.; Arroo, R. R. J.; Tsatsakis, A.; Spandidos, D.
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    Hydroxylation of synthetic methoxylated analogues of the chemopreventative agent resveratrol alters their antiproliferative activity.
    (Spandidos, 2010) Androutsopoulos, Vasilis; Ruparelia, K. C.; Arroo, R. R. J.; Filippakis, H.; Spandidos, D. A.; Tsatsakis, A. M.
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    The Methoxylated Flavones Eupatorin and Cirsiliol Induce CYP1 Enzyme Expression in MCF7 Cells.
    (ACS, 2009-07-14) Androutsopoulos, Vasilis; Arroo, R. R. J.; Li, N. C.
    Flavonoids have often been associated with cancer prevention and activity of the human cytochrome P450 enzymes CYP1A1 and CYP1B1 with the occurrence of cancer. The flavones eupatorin (1) and cirsiliol (2) enhanced CYP1 enzyme activity in a concentration-dependent manner in MCF7 human breast adenocarcinoma cells. In the range of 0−2.5 μM, 2 caused a dose-dependent increase in CYP1B1 mRNA levels and an increase in CYP1A1 mRNA. Compound 1 caused an increase in CYP1A1 and CYP1B1 mRNA at higher doses ( 5 μM). Both CYP1B1 and CYP1A1 catalyzed the conversion of 2 into an as yet unidentified compound. Application of the CYP1 family inhibitor, acacetin, significantly increased the IC50 value of 2 in MCF7 cells, but did not significantly affect the action of 1. The data suggest that 2 induces CYP1 enzyme expression in cancer cells and is subsequently converted by CYP1B1 or CYP1A1 into an antiproliferative agent.
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    Natural substrates and inhibitors of CYP1 family enzymes
    (De Montfort University, 2006) Androutsopoulos, Vasilis
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    Phytoestrogens as natural prodrugs in cancer prevention - a novel concept
    (Springer, 2008) Arroo, R. R. J.; Androutsopoulos, Vasilis; Patel, A.; Surichan, Somchaiya; Wilsher, N.; Potter, Gerard A.
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    Phytoestrogens as natural prodrugs in cancer prevention: Dietary flavonoids
    (Springer, 2009) Arroo, R. R. J.; Androutsopoulos, Vasilis; Beresford, Kenneth J. M.; Ruparelia, K. C.; Surichan, Somchaiya; Wilsher, N.; Potter, Gerard A.
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    Phytoestrogens as natural prodrugs in cancer prevention: towards a mechanistic model
    (Springer, 2014-06-14) Arroo, R. R. J.; Beresford, Kenneth J. M.; Bhambra, Avninder S.; Boarder, M. R.; Budriesi, Roberta; Cheng, Zhong; Micucci, Matteo; Ruparelia, K. C.; Surichan, Somchaiya; Androutsopoulos, Vasilis
    It has been widely acknowledged that regular consumption of fresh fruits and vegetables is linked with a relatively low incidence of cancers (e.g. breast, cervix, and colon). Notably, dietary polyphenolic compounds that show some structural similarity to human estrogen, e.g. isoflavones, coumestans, lignans, flavones, have been proposed to play a role in cancer prevention. However, at present there is no satisfactory explanation for the cancer preventative properties of this group of compounds. Whereas polyphenolic compounds have been shown to inhibit proliferation of tumour cells in vitro, the results of in vivo tests have mostly been disappointing in this respect. It seems that mammalian phase II detoxification mechanisms make that dietary polyphenols are rapidly and effectively removed from the body, i.e. their concentration in the blood plasma hardly ever reaches levels high enough to have a possible effect on tumour growth. The polymethoxyflavones nobiletin and tangeretin, common constituents of Citrus peel, are better absorbed than polyhydroxy flavonoids, and maintain their biological activity for a longer period of time. The compounds are known to be substrates for the estrogen-converting cytochrome P450 enzymes CYP1A1 and CYP1B1, which are typically overexpressed in a range of tumour tissues. The enzymes catalyse regioselective hydroxylation and dealkylation of the polymethoxyflavones, resulting in reaction products that appear to inhibit cell proliferation via interference with the MAPK/ERK cell signalling pathway.