MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer.

ABSTRACT: Sirtuin 6 (SIRT6), a member of the sirtuin family, is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase that is involved in various physiological and pathological processes. SIRT6 is generally downregulated and linked to tumorigenesis in non-small cell lung carcinoma (NSCLC), thus regarded as a promising therapeutic target of NSCLC. In this study, we investigated whether MDL-800, an allosteric activator of SIRT6, exerted antiproliferation effect against NSCLC cells in vitro and in vivo. We showed that MDL-800 increased SIRT6 deacetylase activity with an EC₅₀ value of 11.0 ± 0.3 μM; MDL-800 (10-50 μM) induced dose-dependent deacetylation of histone H3 in 12 NSCLC cell lines. Treatment with MDL-800 dose dependently inhibited the proliferation of 12 NSCLC

SUBMITTER: Shang JL 

PROVIDER: S-EPMC7921659 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature