Phorbol esters attenuate the expression of p53 in cells treated with doxorubicin and protect ts-p53/K562 from apoptosis

Phorbol Esters Attenuate the Expression of p53 in Cells Treated with Doxorubicin and Protect ts-p53/K562 from Apoptosis L. Magnelli, M. Cinelli, V. Chiarugi Univ Florence, Inst Gen Pathol, Molec Biol Lab, I 50134 Florence, Italy Available online 22 April 2002. http://dx.doi.org/10.1006/bbrc.1995.2512, How to Cite or Link Using DOI Cited by in Scopus (24) Permissions & Reprints 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°C, but behaves in a wild-type fashion at 32°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.