Journal
BIOMOLECULES
Volume 12, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/biom12020276
Keywords
TP53; PDAC; berberine; NAX compounds; mutant TP53 reactivators
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Funding
- East Carolina University [111104, 111110-668715-0000]
- Fondazione del Monte di Bologna e Ravenna Research grant
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The study indicates that TP53 reactivator APR-246 can increase the therapeutic potential of many modified berberine compounds, which is of significance for pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. In similar to 75% of PDAC, the tumor suppressor TP53 gene is mutated. Novel approaches to treat cancer involve compounds called mutant TP53 reactivators. They interact with mutant TP53 proteins and restore some of their growth suppressive properties, but they may also interact with other proteins, e.g., TP63 and TP73. We examined the ability of the TP53 reactivator APR-246 to interact with eleven modified berberine compounds (NAX compounds) in the presence and absence of WT-TP53 in two PDAC cell lines: the MIA-PaCa-2, which has gain of function (GOF) TP53 mutations on both alleles, and PANC-28, which lacks expression of the WT TP53 protein. Our results indicate the TP53 reactivator-induced increase in therapeutic potential of many modified berberines.
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