Tamoxifen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG2 via down-regulation of telomerase activity

• Published in: Liver international 2004-02, Vol.24 (1), p.46-54
• Main Authors: Brandt, Sebastian, Heller, Hartmut, Schuster, Klaus-Dieter, Grote, Jürgen
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Hormonal - pharmacology; apoptosis; Apoptosis - drug effects; Cell Count; Cell Cycle - drug effects; Cell Line, Tumor; Cell Physiological Phenomena - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Down-Regulation - drug effects; estrogen receptor; Hepatoblastoma - drug therapy; Hepatoblastoma - pathology; hepatoma; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Reverse Transcriptase Inhibitors - pharmacology; tamoxifen; Tamoxifen - pharmacology; telomerase; Telomerase - drug effects; Telomerase - physiology; Time Factors; Zidovudine - pharmacology
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2004.00887.x

: 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.