Liver international : official journal of the International Association for the Study of the Liver · 2004
Tamoxifen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG2 via down-regulation of telomerase activity.
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Brandt Sebastian, Heller Hartmut, Schuster Klaus-Dieter, Grote Jürgen
Аннотация
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.
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.