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|Title:||Tamoxifen inhibits nitrobenzylthioinosine-sensitive equilibrative uridine transport in human MCF-7 breast cancer cells||Authors:||Cai, J.
|Issue Date:||15-Dec-1996||Citation:||Cai, J., Lee, C.W. (1996-12-15). Tamoxifen inhibits nitrobenzylthioinosine-sensitive equilibrative uridine transport in human MCF-7 breast cancer cells. Biochemical Journal 320 (3) : 991-995. ScholarBank@NUS Repository.||Abstract:||Tamoxifen inhibits the binding of [3H] nitrobenzylthioinosine ([3H]NBMPR) to human MCF-7 breast cancer cells with an IC50 of 8 μM. Tamoxifen at 30 μM changed the apparent K(d) for [3H]NBMPR binding from 0.63 ± 0.12 to 4.75 ± 0.58 nM, with little effect on the B(max) (311,000 ± 76,000 and 263,000 ± 46,000 sites per cell for untreated and tamoxifen-treated cells respectively). Corresponding to this decrease in binding of [3H]NBMPR in the presence of tamoxifen was an inhibition of NBMPR-sensitive equilibrative transport of 50 μM [3H]urddine (IC50 7-10 μM). In the presence of 15 μM tamoxifen, the apparent K(m) for [3H]uridine transport was increased from 390 ± 30 to 1500 ± 250 μM, with no change in V(max) (12.0 ± 0.1 and 11.3 ± 4.3 μM/s for untreated and tamoxifen-treated cells respectively). The inhibitory effect of tamoxifen on NBMPR-sensitive equilibrative uridine transport was specific, as similar results were also observed in HL-60 leukaemia and EL4 lymphoma cells. Furthermore a similar concentration of tamoxifen had no effect on the NBMPR-insensitive equilibrative transport of uridine in MCF-7, HL-60 and Morris 7777 hepatoma cells, and on the Na+-dependent transport of uridine in murine splenocytes. In this paper we demonstrate that tamoxifen by itself might have some antiproliferative effects through inhibition of DNA synthesis by blocking the nucleoside salvage pathway.||Source Title:||Biochemical Journal||URI:||http://scholarbank.nus.edu.sg/handle/10635/133997||ISSN:||02646021|
|Appears in Collections:||Staff Publications|
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