Tenovin-1, functioning as a p53 activator, shields p53 from degradation facilitated by MDM2. Its mechanism involves the inhibition of protein deacetylating activities of SirT1 and SirT2. Additionally, Tenovin-1 serves as an inhibitor of dihydroorotate dehydrogenase (DHODH)[1][2].
体内研究
Tenovin-1 (92 mg/kg, i.p.) suppresses tumor growth in SCID mice originating from BL2 cells or ARN8 cells[5].
体外研究
Tenovin-1 shields p53 from degradation mediated by MDM2, while minimally affecting p53 synthesis. It targets factor(s) upstream of p53, influencing not only p53 function but also other cellular pathways. At a concentration of 10 μM, Tenovin-1 inhibits the deacetylase activity of SirT2[1].
Tenovin-1 (1-10 μM) elicits a concentration-dependent, bell-shaped cell death response in SK-N-MC cells. It modulates the gene and protein expression of Bcl-2 family members, exhibiting a more pronounced effect on mRNA and protein expression at lower concentrations compared to higher ones. Additionally, Tenovin-1-induced cytotoxicity in p53 wild-type WE-68 cells relies on caspases, whereas it is independent of caspases in p53 null SK-N-MC cells. AIF predominantly contributes to Tenovin-1-induced cell death in p53 null SK-N-MC cells, whereas in p53 wild-type WE-68 cells, its role is less significant. Furthermore, reactive oxygen species participate in Tenovin-1-mediated cell death in SK-N-MC cells. Moreover, Tenovin-1 induces DNA damage in SK-N-MC cells[3].
Tenovin-1 (5 μM) enlarges the nuclear size in both glioblastoma cells and rat primary astrocytes. Furthermore, Tenovin-1 induces cellular senescence, a process seemingly independent of cell death[4].
Tenovin-1 (10 μM) diminishes the proliferation and anchorage-independent growth of NSCLC cells. Moreover, it impedes the growth of H358 lung cancer cells[5].
Tenovin-1 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
MCF7 cells
10 μM
Function assay
6 h
Inhibition of SirT1 assessed as increase in p53 expression in human MCF7 cells at 10 uM after 6 hrs by Western blotting
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