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EX527, a Sirt-1 inhibitor, induces apoptosis in glioma via activating the p53 signaling pathway.
Wang, Tianpeng; Li, Xiaoxi; Sun, Shu-Lan.
Afiliación
  • Wang T; Department of Radiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute.
  • Li X; Central laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, People's Republic of China.
  • Sun SL; Central laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, People's Republic of China.
Anticancer Drugs ; 31(1): 19-26, 2020 01.
Article en En | MEDLINE | ID: mdl-31490284
ABSTRACT
Sirtuin-1 (Sirt-1), an NAD-dependent deacetylase, promotes tumorigenesis in glioma; however, whether the Sirt-1 specific inhibitor, EX527 exerts antitumor effects and the underlying mechanism in glioma requires further investigation. In the present study, the proliferative and colony formation abilities of two glioma cell lines (U87MG and LN-299) were inhibited by EX527. Treatment with EX527 increased the number of apoptotic cells (Annexin V-fluorescein isothiocyanate/propidium iodide); pretreatment with the caspase inhibitor Z-VAD-FMK suppressed EX527-induced apoptosis, suggesting that EX527 induced caspase-dependent apoptosis. In addition, western blotting revealed that EX527 treatment increased the expression of cleaved-caspase-3, poly (ADP-ribose) polymerase-1, B-cell lymphoma 2 (Bcl-2)-associated-X-protein and Bcl-2-like 11 but decreased that of Bcl-2. p53 is deacetylated by Sirt-1, attenuating its function. Furthermore, EX527 upregulated the expression of p53, acetylated p53 and the p53 target gene p21. This result suggests that EX527 induced cell apoptosis by activating p53 in glioma. Of note, EX527 exhibited antitumor effects on patient-derived glioma cells under three-dimensional culture conditions. Collectively, the results of the present study indicated that EX527 may be used as an effective compound in the treatment of glioma.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carbazoles / Proteína p53 Supresora de Tumor / Sirtuina 1 / Glioma Límite: Humans Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carbazoles / Proteína p53 Supresora de Tumor / Sirtuina 1 / Glioma Límite: Humans Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2020 Tipo del documento: Article