Pharmacological activation of SIRT6 suppresses progression of head and neck and esophageal squamous cell carcinoma by modulation of cellular metabolism and protein translation.

ABSTRACT: Sirtuin 6 (SIRT6), a NAD+-dependent histone deacetylase, has been shown to function as a tumor suppressor in several cancer types, including squamous cell carcinoma of the head and neck and the esophagus (HNSCC and ESCC). However, the potential of therapies involving the activation of SIRT6 in HNSCC and ESCC remains unexplored. In this work, we investigated the therapeutic potential and mechanisms of action of the allosteric SIRT6 activator MDL-800 in HNSCC and ESCC models. MDL-800 treatment inhibited the proliferation and migration of HNSCC and ESCC cell lines in vitro, and delayed tumor growth in cell-derived xenograft models, in vivo. Mechanistically, global H3K9ac acetylation profiling and protein arrays demonstrated that MDL-800 treatment potently inhibits glucose metabolism and prote

SUBMITTER: Ben Lulu T 

PROVIDER: S-EPMC12533074 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature