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


CONCLUSIONS
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.
Brandt
Sebastian
S
Department of Physiology, University of Bonn, Bonn, Germany. sebastian.brandt@uni-bonn.de
Heller
Hartmut
H
Schuster
Klaus-Dieter
KD
Grote
Jürgen
J
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*; D019098:Telomerase / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D015215:Zidovudine / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D018894:Reverse Transcriptase Inhibitors; D013629:Tamoxifen; D015215:Zidovudine; D019098:Telomerase