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  • Title: Tamoxifen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG2 via down-regulation of telomerase activity.
    Author: Brandt S, Heller H, Schuster KD, Grote J.
    Journal: Liver Int; 2004 Feb; 24(1):46-54. PubMed ID: 15102000.
    Abstract:
    BACKGROUND/AIMS: Antiproliferative action of tamoxifen in the estrogen receptor-alpha-negative human hepatoblastoma cell line HepG2 was investigated. METHODS: HepG2 cells, seeded at different densities (4000-36 000 cells/cm(2)), were incubated with tamoxifen (1, 10, or 20 microM) or the telomerase inhibitor 3'-azido-3'-deoxythymidine (AZT) (0.6-3.0 mM) up to 72 h. Cell viability was assessed (MTT-test), flow cytometric analysis was performed, and telomerase activity was measured (telomeric repeat amplification protocol assay). RESULTS: Ten or 20 microM tamoxifen induced a reduction of cell viability. Basically reduction of viability was related to an increase in the fraction of G0/1-phase. When tamoxifen was present at higher concentration (20 microM) or at low cell density (4000/cm(2)) an additional increase of the rate of apoptotic cells occurred with a delay, aggravating the effect of tamoxifen on cell viability substantially. When apoptosis was induced a significant suppression of telomerase activity preceded regularly. Direct inhibition of telomerase activity with AZT resulted in a decrease of cell viability and apoptosis. CONCLUSION: The tamoxifen-induced reduction of cell viability in HepG2 cells depends on drug concentration and cell density and is due to cytostatic and cytocide effects. The latter may be mediated by a down-regulation of telomerase activity.
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