Cell cycle arrest in ovarian cancer cell lines does not depend on p53 status upon treatment with cytostatic drugs.
Human ovarian cancer cell lines with different p53 status were investigated for p53-dependency of cell cycle arrest upon treatment with cytostatic drugs. For this purpose commonly used anti-cancer drugs and a novel anti-cancer drug, gemcitabine, were applied. Cell cycle arrest was dependent on the drug dose used, as observed for all anti-cancer drugs applied, but not related to functional p53. With the exception of the etoposide-effected G2/M arrest at high concentrations, which seems to depend on functional p53, since it did not occur in cells with inactive p53. Only in cells with wt p53 and quasi-wild-type, p53 accumulated in the nucleus upon drug treatment with all anti-cancer agents applied. The level of accumulation was drug dose-dependent for each drug tested. The accumulated p53 was biochemically active, as measured in a transient transfection assay upon treatment with gemcitabine, cisplatin, etoposide, and Taxol. Activity was dependent on the drug dose applied and proportional to the level of accumulated p53, except for Taxol-induced p53 accumulation which correlated inversely with p53 biochemical activity. Apoptosis was estimated by in situ end labeling by biotinylated dUTP with the terminal deoxyribonucleotidyl transferase assay. Apoptosis occured after arrest at the various phases of the cell cycle in all cell lines tested, depending on the drug and the drug dose used. Nevertheless, cells with wt p53 exhibited the highest fraction of apoptotic cells.
Abteilung Virologie, Institut fur Medizinische Mikrobiologie und Hygiene der Universitat Freiburg, D-79104 Freiburg, Germany.
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Merlin
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Brandner
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Hess
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D003841:Deoxycytidine; D000093542:Gemcitabine