Dual inhibition of BET and HAT/p300 suppresses colorectal cancer via DR5- and p53/PUMA-mediated cell death.

ABSTRACT:

Background

Colorectal cancer (CRC) frequently has a dysregulated epigenome causing aberrant up-regulation of oncogenes such as c-MYC. Bromodomain and extra-terminal domain (BET) proteins and histone acetyltransferases (HAT) are epigenetic regulatory proteins that create and maintain epigenetic states supporting oncogenesis. BET inhibitors and HAT inhibitors are currently being investigated as cancer therapeutics due to their ability to suppress cancer-promoting epigenetic modifiers. Due to the extensive molecular crosstalk between BET proteins and HAT proteins, we hypothesized that dual inhibition of BET and HAT could more potently inhibit CRC cells than inhibition of each individual protein.

Methods

We investigated the activity and mechanisms of a dual BET and HAT inhibitor

SUBMITTER: Kuang C 

PROVIDER: S-EPMC9599411 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature