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• W2741661609 abstract "ABSTRACTP53 tumor suppressor gene mutations occur in the majority of human cancers and contribute to tumor development, progression and therapy resistance. Direct functional restoration of p53 as a transcription factor has been difficult to achieve in the clinic. We performed a functional screen using a bioluminescence-based transcriptional read-out to identify small molecules that restore the p53 pathway in mutant p53-bearing cancer cells. We identified CB002, as a candidate that restores p53 function in mutant p53-expressing colorectal cancer cells and without toxicity to normal human fibroblasts. Cells exposed to CB002 show increased expression of endogenous p53 target genes NOXA, DR5, and p21 and cell death which occurs by 16 hours, as measured by cleaved caspases or PARP. Stable knockdown of NOXA completely abrogates PARP cleavage and reduces sub-G1 content, implicating NOXA as the key mediator of cell death induction by CB002. Moreover, CB002 decreases the stability of mutant p53 in RXF393 cancer ce..." @default.
• W2741661609 created "2017-08-08" @default.
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• W2741661609 date "2018-02-19" @default.
• W2741661609 modified "2023-10-06" @default.
• W2741661609 title "CB002, a novel p53 tumor suppressor pathway-restoring small molecule induces tumor cell death through the pro-apoptotic protein NOXA" @default.
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• W2741661609 doi "https://doi.org/10.1080/15384101.2017.1346762" @default.
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