Tamoxifen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG2 via down-regulation of telomerase activity
Article first published online: 18 FEB 2004
Volume 24, Issue 1, pages 46–54, February 2004
How to Cite
Brandt, S., Heller, H., Schuster, K.-D. and Grote, J. (2004), Tamoxifen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG2 via down-regulation of telomerase activity. Liver International, 24: 46–54. doi: 10.1111/j.1478-3231.2004.00887.x
- Issue published online: 18 FEB 2004
- Article first published online: 18 FEB 2004
- Received 14 May 2003, accepted 25 September 2003
- estrogen receptor;
Background/Aims: Antiproliferative action of tamoxifen in the estrogen receptor-α-negative human hepatoblastoma cell line HepG2 was investigated.
Methods: HepG2 cells, seeded at different densities (4000–36 000 cells/cm2), were incubated with tamoxifen (1, 10, or 20 μM) 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 μM 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 μM) or at low cell density (4000/cm2) 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 apoptotis.
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.