PRIMA-1 inhibits Y220C p53 amyloid aggregation and synergizes with cisplatin in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Although many therapeutic options are available, several factors, including the presence of p53 mutations, impact tumor development and therapeutic resistance. TP53 is the second most frequently mutated gene in HCC, comprising more than 30% of cases. Mutations in p53 result in the formation of amyloid aggregates that promote tumor progression. The use of PRIMA-1, a small molecule capable of restoring p53, is a therapeutic strategy to pharmacologically target the amyloid state mutant p53. In this study, we characterize an HCC mutant p53 model for the study of p53 amyloid aggregation in HCC cell lines, from in silico analysis of p53 mutants to a 3D-cell culture model and demonstrate the unpre

SUBMITTER: Paz MM 

PROVIDER: S-EPMC10123287 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature