Effect of doxorubicin on telomerase activity and apoptotic gene expression in doxorubicin-resistant and -sensitive MCF-7 cells

Eskiocak U., Iseri O. D., Kars M. D., Bicer A., GÜNDÜZ U.

CHEMOTHERAPY, vol.54, no.3, pp.209-216, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 54 Issue: 3
  • Publication Date: 2008
  • Doi Number: 10.1159/000140464
  • Journal Name: CHEMOTHERAPY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.209-216
  • Keywords: doxorubicin, telomerase, Bcl-2, Bcl-x(L), Bax, MCF-7, MDR, IN-VITRO, DRUG-RESISTANCE, RNA EXPRESSION, BREAST-CANCER, ACTIVATION, PROTEIN, BCL-2, ASSAY, CHEMOSENSITIVITY, INHIBITION
  • Middle East Technical University Affiliated: Yes

Abstract

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.