Sirtuin1 activator SRT2183 suppresses glioma cell growth involving activation of endoplasmic reticulum stress pathway

摘要: Glioblastoma (GBM) is an extremely deadly form of brain cancer with limited treatment options and thus novel therapeutic modalities are necessary. Histone deacetylase inhibitors (HDACi) have demonstrated clinical preclinical activities against GBM. (Silent mating type information regulation 2 homolog, Sirt1) abbreviated as Sirtuin 1, has been implicated in We explored the activity Sirt1 activator SRT2183 glioma cell lines terms biological response. The effects on growth neurosphere survival were evaluated vitro using CCK-8, clonogenic assays, respectively. Glioma cycle arrest apoptosis determined by flow cytometry. SRT2183-induced autophagy was investigated detection GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, conversion nonlipidated LC3 (LC3-I) to phosphatidylethanolamine-conjugated (LC3-II). Acetylation STAT3 NF-κB SRT2183-treated cells examined immunoprecipitation. expression levels anti-apoptotic proteins assayed immunoblotting. suppressed destroyed neurospheres vitro. Furthermore, induced apoptosis, accompanying upregulation pro-apoptotic Bim downregulation Bcl-2 Bcl-xL. Notably, ER stress triggered upon exposure while pre-exposure 4-PBA, inhibitor, significantly antagonized SRT2183-mediated inhibition cells. In addition, pharmacological modulation appeared not affect SRT2183-inhibited growth. Of interest, acetylation phosphorylation p65 differentially affected SRT2183. Our data suggest pathway involved glioma. Further investigation vivo needed consolidate data.