E-GEOD-35972 - Transcription profiling by array of ovarian carcinoma TOV-112D cells treated with NSC319726 to investigate the effect on p53 targets
Released on 22 February 2012, last updated on 16 April 2013
Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. We utilized gene expression microarrays to examine the transcriptional activity of p53 targets in TOV112D cells after treatment with NSC319726. Triplicate cultures of TOV112D cells untreated, treated with NSC319726. Total RNA was extracted and hybridized to Affymetrix human U133 plus 2.0 microarrays.
transcription profiling by array
Alexei Vazquez <email@example.com>, Darren Carpizo, Xin Yu
Allele-specific p53 mutant reactivation. Yu X, Vazquez A, Levine AJ, Carpizo DR.