Treatment of Terminal Peritoneal Carcinomatosis by a Transducible p53-Activating Peptide (original) (raw)
Figure 2
RI-TATp53C′ Peptide Activates p53-Dependent Transcription and Inhibits Tumor Cells Expressing p53
(A, left) Induction of transcription from a p53-dependent promoter by RI-TATp53C′ only when p53 protein is expressed. H1299 cells (p53−/−) were cotransfected with p53-responsive reporter (PG13-Luc) and either empty vector or p53 expression vector. Depicted are mean and standard deviation of triplicate results that are representative of multiple experiments.
(A, right) RI-TATp53C′ peptide activates p53-dependent transcription in cells expressing DNA contact mutant p53. SW480 cells containing a DNA contact mutant (R273H) p53 were transfected with p53-dependent reporter (PG13-Luc). H1299 cells (_p53_−/−) were co-transfected with PG13-Luc and either R248Q or R273H mutant p53 expression vector. RI-TATp53C′ was added to cells, and promoter activity was assessed 24 h later.
(B) Inhibition of tumor cell proliferation in a p53-dependent manner by RI-TATp53C′. Increasing concentrations of peptide were added to HCT 116 cells (p53+/+) and their p53−/− isogenic derivatives. After 2 d, the number of viable cells was assessed by Trypan blue exclusion and normalized to the number of viable untreated cells. Mean and standard deviation of multiple experiments are depicted.
(C) Inhibition of the proliferation of tumor cells expressing wild-type or mutant p53, but not p53−/− tumor cells or nontransformed human fibroblasts. Cell viability was assessed as in (B). Mean and standard deviation of multiple experiments are depicted.