NAD(P)H: quinone oxidoreductase enhances proliferation inhibition by 4-hydroxytamoxifen |
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Authors: | Allen Peter G Kolesar Jill M |
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Institution: | School of Pharmacy, University of Wisconsin-Madison, 53705-2222, USA. |
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Abstract: | The nonquinone compound, 4-OHT, was identified as a NQOR substrate as measured by reduction in the M7T assay. 4-OHT was then evaluated for effects on proliferation inhibition in two independent cell model systems, the MCF7 (NQO1+), MCF7 + dicoumarol (NQO1-) and the CHO (NQO1-) CHO-812 (NQO1+). NQOR activity predicts inhibition of proliferation by 4-OHT in these two models MCF7s were more sensitive to 4-OH tamoxifen with a PI50 of 2.65 nM than MCF-7 + dicoumarol with a PI50 of 1.84 microM (p<0.05, by one way ANOVA). CHO812s were also more sensitive to proliferation inhibition by 4-OH tamoxifen with a PI50 of 80.2 microM compared to the CHOs with a PI50 of 93.1 microM (p<0.05, by one-way ANOVA). Suggesting: 1) 4-OH tamoxifen is reduced by NQOR and 2) the reduced product is more active than the parent compound. |
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