Histone Acetyltransferase (HAT) P300/CBP Inhibitors Induce Synthetic Lethality in PTEN-Deficient Colorectal Cancer Cells through Destabilizing AKT.

ABSTRACT: PTEN, a tumor suppressor, is found loss of function in many cancers, including colorectal cancer. To identify the synthetic lethal compounds working with PTEN deficiency, we performed a synthetic lethality drug screening with PTEN-isogenic colorectal cancer cells. From the screening, we found that PTEN^-/- colorectal cancer cells were sensitive to anacardic acid, a p300/CBP histone acetyltransferase (HAT) inhibitor. Anacardic acid significantly reduced the viability of PTEN^-/- cells not in PTEN^+/+ cells via inducing apoptosis. Inhibition of HAT activity of p300/CBP by anacardic acid reduced the acetylation of histones at the promoter region and inhibited the transcription of Hsp70 family of proteins. The down-regulation of Hsp70 family p

SUBMITTER: Liu Y 

PROVIDER: S-EPMC7211175 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature