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Cell cycle effects of topotecan alone and in combination with irradiation.
- Source :
-
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2005 May; Vol. 75 (2), pp. 237-45. - Publication Year :
- 2005
-
Abstract
- Background and Purpose: To elucidate the role of TP53 on differential effects of topoisomerase I inhibitor topotecan (Hycamtin on radiation sensitivity.<br />Materials and Methods: Cell cycle distribution and protein expression of TP53, p21(WAF1/CIP1) and cyclin B was studied in CCD32 lung fibroblasts, glioblastoma cell lines U118 (mutant TP53), and U87 (wildtype TP53) after treatment with topotecan (0.05 and 1 microM) and/or ionizing radiation (2 Gy).<br />Results: Cell cycle effects varied with topotecan concentration, resulting in G1 arrest (1 microM), or S/G2/M arrest (0.05 microM), and was modified differentially in fibroblasts and in glioblastoma cells in combination with irradiation. Phosphorylation of TP53 and expression of p21(WAF1/CIP1) was induced by IR and/or topotecan in CCD32 cells, and in U118 cells after topotecan treatment, accompanied by cyclin B degradation. In U87 cells only 1 microM topotecan generated phosphorylation of TP53 and p21(WAF1/CIP1) expression; 0.05 microM caused stabilization of cyclin B.<br />Conclusions: The antagonistic effect of combined topotecan/irradiation treatment in fibroblasts was most likely due to an immediate radiation induced G1 arrest, but was not observed in p53 wildtype glioblastoma cells. Thus, the impact of TP53 on the topotecan response remains indistinct, and is obviously influenced by other genomic alterations acquired by tumor cells.
- Subjects :
- Cell Cycle Proteins biosynthesis
Cell Cycle Proteins genetics
Cell Cycle Proteins physiology
Cyclin B biosynthesis
Cyclin B genetics
Cyclin B physiology
Cyclin-Dependent Kinase Inhibitor p21
Dose-Response Relationship, Drug
Fibroblasts
Gene Expression Regulation, Neoplastic drug effects
Humans
Lung cytology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 physiology
Antineoplastic Agents pharmacology
Cell Cycle drug effects
Cell Cycle radiation effects
Glioblastoma genetics
Glioblastoma pathology
Topotecan pharmacology
Tumor Suppressor Protein p53 biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0167-8140
- Volume :
- 75
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 15890420
- Full Text :
- https://doi.org/10.1016/j.radonc.2005.03.025