title: Phorbol esters attenuate the expression of p53 in cells treated with doxorubicin and protect TS-P53/K562 from apoptosis.
abstract: The induction of p53 by doxorubicin in normal human fibroblasts was completely reverted by TPA, a phorbol ester. A ts-p53 mutant protein which is ineffective at 37 degrees C, but behaves in a wild-type fashion at 32 degrees C, was overexpressed in the p53-null human leukemia cell line K562. Wild-type-p53 overexpression induced apoptosis, whereas TPA protected K562 cells from this phenomena. By analogy with the observed human fibroblasts, TPA was found to decrease p53 amount. The TPA-dependent down-regulation of p53 could explain the chromosomal gross alterations typical of cells subjected to a chronic TPA treatment, alterations also found in cells defective for p53 function.
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D013755:Tetradecanoylphorbol Acetate