Novel Hybrid CHC from β-carboline and N-Hydroxyacrylamide Overcomes Drug-Resistant Hepatocellular Carcinoma by Promoting Apoptosis, DNA Damage, and Cell Cycle Arrest.

ABSTRACT: A novel hybrid CHC was designed and synthesized by conjugating β-carboline with an important active fragment N-hydroxyacrylamide of histone deacetylase (HDAC) inhibitor by an amide linkage to enhance antitumor efficacy/potency or even block drug resistance. CHC displayed high antiproliferative effects against drug-sensitive SUMM-7721, Bel7402, Huh7, and HCT116 cells and drug-resistant Bel7402/5FU cells with IC₅₀ values ranging from 1.84 to 3.27 μM, which were two-to four-fold lower than those of FDA-approved HDAC inhibitor SAHA. However, CHC had relatively weak effect on non-tumor hepatic LO2 cells. Furthermore, CHC exhibited selective HDAC1/6 inhibitory effects and simultaneously augmented the acetylated histone H3/H4 and α-tubulin, which may make a great contribution to

SUBMITTER: Miao J 

PROVIDER: S-EPMC7848139 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature