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Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic P388 and P388/R84 cells.
Anticancer Res. 1997 Sep-Oct; 17(5A):3369-76.AR

Abstract

The induction of apoptosis by doxorubicin (DOX) alone or in the presence of efflux blockers, verapamil (VPL) or trifluoperazine (TFP), and of bcl-2 and mdr-1 gene expression was analyzed in murine leukemic P388 and doxorubicin resistant P388/R84 cells. Incubation with DOX (0.1-1 microM) for 24 hours induced apoptosis in sensitive cells but not in the resistant P388/R84 cells. Flow cytometric analysis of apoptosis by terminal dideoxynucleotidyl (TdT) assay showed that 1 microM DOX induced apoptosis in 70% of P388 cells and in less than 5% of P388/R84 cells. When P388/R84 resistant cells were co-incubated with DOX and efflux blockers (10 microM VPL or 15 microM TFP), enhanced cellular DOX accumulation was accompanied by apoptosis. Quantitative analysis of DNA fragmentation by 14C-thymidine incorporation and gel electrophoresis of fragmented DNA confirmed the results from TdT assay and showed enhancement of DOX-induced DNA fragmentation in the presence of efflux blockers (VPL or TFP). DOX + VPL and DOX + TFP combination treatments induced apoptosis in upto 55% and 83% of P388/R84 cells, respectively. mdr-1 mRNA and P-gp expression were not altered during DOX-induced apoptosis. The results suggest that in murine leukemic cells, down-regulation of bcl-2 mRNA expression occurs during DOX-induced apoptosis and it depends on the cellular drug retention determined by mdr-1/P-gp drug efflux.

Authors+Show Affiliations

Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, FL 33136, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9413174

Citation

Ramachandran, C, et al. "Bcl-2 and Mdr-1 Gene Expression During Doxorubicin-induced Apoptosis in Murine Leukemic P388 and P388/R84 Cells." Anticancer Research, vol. 17, no. 5A, 1997, pp. 3369-76.
Ramachandran C, You W, Krishan A. Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic P388 and P388/R84 cells. Anticancer Res. 1997;17(5A):3369-76.
Ramachandran, C., You, W., & Krishan, A. (1997). Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic P388 and P388/R84 cells. Anticancer Research, 17(5A), 3369-76.
Ramachandran C, You W, Krishan A. Bcl-2 and Mdr-1 Gene Expression During Doxorubicin-induced Apoptosis in Murine Leukemic P388 and P388/R84 Cells. Anticancer Res. 1997 Sep-Oct;17(5A):3369-76. PubMed PMID: 9413174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic P388 and P388/R84 cells. AU - Ramachandran,C, AU - You,W, AU - Krishan,A, PY - 1997/12/31/pubmed PY - 1997/12/31/medline PY - 1997/12/31/entrez SP - 3369 EP - 76 JF - Anticancer research JO - Anticancer Res. VL - 17 IS - 5A N2 - The induction of apoptosis by doxorubicin (DOX) alone or in the presence of efflux blockers, verapamil (VPL) or trifluoperazine (TFP), and of bcl-2 and mdr-1 gene expression was analyzed in murine leukemic P388 and doxorubicin resistant P388/R84 cells. Incubation with DOX (0.1-1 microM) for 24 hours induced apoptosis in sensitive cells but not in the resistant P388/R84 cells. Flow cytometric analysis of apoptosis by terminal dideoxynucleotidyl (TdT) assay showed that 1 microM DOX induced apoptosis in 70% of P388 cells and in less than 5% of P388/R84 cells. When P388/R84 resistant cells were co-incubated with DOX and efflux blockers (10 microM VPL or 15 microM TFP), enhanced cellular DOX accumulation was accompanied by apoptosis. Quantitative analysis of DNA fragmentation by 14C-thymidine incorporation and gel electrophoresis of fragmented DNA confirmed the results from TdT assay and showed enhancement of DOX-induced DNA fragmentation in the presence of efflux blockers (VPL or TFP). DOX + VPL and DOX + TFP combination treatments induced apoptosis in upto 55% and 83% of P388/R84 cells, respectively. mdr-1 mRNA and P-gp expression were not altered during DOX-induced apoptosis. The results suggest that in murine leukemic cells, down-regulation of bcl-2 mRNA expression occurs during DOX-induced apoptosis and it depends on the cellular drug retention determined by mdr-1/P-gp drug efflux. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/9413174/Bcl_2_and_mdr_1_gene_expression_during_doxorubicin_induced_apoptosis_in_murine_leukemic_P388_and_P388/R84_cells_ L2 - http://www.komp.org/ncbi.php?PMID=9413174 DB - PRIME DP - Unbound Medicine ER -