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Effect of doxorubicin on telomerase activity and apoptotic gene expression in doxorubicin-resistant and -sensitive MCF-7 cells
Date
2008-01-01
Author
Eskiocak, Ugur
Iseri, Ozlem Darcansoy
Kars, Meltem Demirel
Bicer, Atilla
Gündüz, Ufuk
Metadata
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This work is licensed under a
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
.
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Background: Dose-and time-dependent effects of doxorubicin on telomerase activity ( TA) and expression levels of hTERT, Bcl-2, Bcl-x(L) and Bax were investigated in doxorubicin-resistant and -sensitive MCF-7 cells. Methods: Doxorubicin-resistant MCF-7/R was developed from sensitive MCF-7 breast carcinoma cell line and acquired resistance was demonstrated by XTT and mRNA analysis of MDR1 and MRP1 genes. Expression levels were determined by RT-PCR. Newly developed rapid and simple TRAP-silver staining assay was used to assess TA levels. Results: Doxorubicin-selected MCF-7 cells were 107-fold resistant to the drug and overexpress MDR1 and MRP1 genes. 72 h doxorubicin incubation caused a decrease in TA in parallel with a small decrease in hTERT level in both sensitive and resistant cells. Bcl-2 expression level decreased upon doxorubicin application in sensitive cells. However, the Bcl-x(L) level increased in sensitive cells after 72 h of doxorubicin incubation. Conclusion: This report demonstrates the inhibitory effects of doxorubicin on TA in both resistant and sensitive MCF-7 cells possibly through modulation of the apoptotic pathway genes. Copyright (C) 2008 S. Karger AG, Basel.
Subject Keywords
Doxorubicin
,
Telomerase
,
Bcl-2
,
Bcl-X(L)
,
Bax
,
MCF-7
,
MDR
URI
https://hdl.handle.net/11511/31459
Journal
CHEMOTHERAPY
DOI
https://doi.org/10.1159/000140464
Collections
Graduate School of Natural and Applied Sciences, Article