Tenovin-6, an analog of Tenovin-1, is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC50s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH)[1].[2].
体内研究
Administered at 50 mg/kg intraperitoneally, it effectively inhibits tumor growth in mice[1].
体外研究
Tenovin-6 inhibits S. cerevisiae growth at an IC50 of 30 μM, showcasing greater toxicity to yeast compared to the less water-soluble Tenovin-1. Tenovin-6 notably elevates endogenous K382-Ac p53 levels in MCF-7 cells rapidly[1].
Tenovin-6, across a range of concentrations from 0 to 15 μM, dose-dependently elevates the level of LC3-II in various cell types, with this increase being dependent on ATG5/7. This treatment not only augments the quantity and brightness of autophagic vesicles, regardless of Torin 1 presence, but also blocks the Torin 1-induced degradation of SQSTM1/p62[3].
When applied at doses between 0, 1, 2.5, 5, and 10 μM, Tenovin-6 significantly curtails cell proliferation in a dose- and time-specific manner across OCI-Ly1, DHL-10, U2932, RIVA, HBL1, and OCI-Ly10 cell lines. It notably boosts the level of LC3B-II in DLBCL cell lines by obstructing the classical autophagy pathway, independently of SIRT1/2/3 and p53 activities, and propels apoptosis via the extrinsic cell-death pathway[4]. Furthermore, Tenovin-6 curbs the growth of UM cells, displaying IC50 values of 12.8 μM, 11.0 μM, 14.58 μM, and 9.62 μM for the 92.1, Mel 270, Omm 1, and Omm 2.3 cells, respectively[5].
Tenovin-6 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Myeloma cells (U266)
4 μM
24 h
Tenovin-6 had minimal effects on the proliferation of U266 cells.
J Pathol. 2017 Jul;242(3):309-321.
human hepatocarcinoma cell line Huh7
5 μM
24 h
Tenovin-6 treatment significantly increased LC3B-II levels in Huh7 cells, and this increase was dose-dependent.
Cell Death Dis. 2017 Feb 9;8(2):e2608.
human lung adenocarcinoma epithelial cell line A549
10 μM
24 h
Tenovin-6 treatment significantly increased LC3B-II levels in A549 cells, and this increase was dose-dependent.
Cell Death Dis. 2017 Feb 9;8(2):e2608.
mouse embryonic fibroblasts (MEFs)
5 μM
24 h
Tenovin-6 significantly increased LC3A/B-II levels in wild-type MEF cells but not in ATG5−/− and ATG7−/− MEF cells.
Cell Death Dis. 2017 Feb 9;8(2):e2608.
chronic lymphocytic leukaemia (CLL) cell
10 µM
24 h
To investigate the cytotoxic effect of Tenovin-6 on CLL cells, results showed that Tenovin-6 induced cell death without significant apoptotic features, and a significant increase in autophagosome number was observed.
Br J Cancer. 2013 Oct 29;109(9):2434-44.
chronic lymphocytic leukaemia (CLL) cell
10 µM
4 h
To investigate the effect of Tenovin-6 on autophagy regulation in CLL cells, results showed that Tenovin-6 inhibited autophagy, leading to an increase in autophagosome number and accumulation of LC3 II and p62/Sequestosome 1.
Br J Cancer. 2013 Oct 29;109(9):2434-44.
Burkitt’s lymphoma cells (BJAB)
4 μM
24 h
Tenovin-6 had minimal effects on the proliferation of BJAB cells.
J Pathol. 2017 Jul;242(3):309-321.
PEL cells (BC3, BCBL-1, BCP1, JSC1)
4 μM
24 h
Tenovin-6 inhibited the proliferation of PEL cells, induced cell cycle arrest and apoptosis.
J Pathol. 2017 Jul;242(3):309-321.
chronic lymphocytic leukemia cells
10 µM
4 h or 24 h
To investigate the effects of Tenovin-6 on CLL cells, it was found to cause cell death through autophagy inhibition rather than inducing apoptosis via the p53 pathway.
Br J Cancer. 2013 Oct 29;109(9):2434-44.
H1650 cells
10 μM
48 h
Tenovin-6 in combination with metformin significantly inhibited cell growth.
J Cell Mol Med. 2019 Apr;23(4):2872-2889.
H460 cells
10 μM
48 h
Tenovin-6 in combination with metformin significantly inhibited cell growth.
J Cell Mol Med. 2019 Apr;23(4):2872-2889.
H1299 cells
10 μM
48 h
Tenovin-6 in combination with metformin significantly inhibited cell growth.
J Cell Mol Med. 2019 Apr;23(4):2872-2889.
A549 cells
10 μM
48 h
Tenovin-6 in combination with metformin inhibited cell proliferation more effectively than either agent alone.
J Cell Mol Med. 2019 Apr;23(4):2872-2889.
Tenovin-6 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NOD/SCID mice
PEL model
Intraperitoneal injection
50 mg/kg
Daily until the end of the experiment
Tenovin-6 significantly inhibited the initiation and progression of PEL and extended the survival of mice.
J Pathol. 2017 Jul;242(3):309-321.
NSG mice
Patient-derived xenograft model
Intraperitoneal injection
50 mg/kg
Twice daily for 3 weeks
Combination therapy of TV-6 with gefitinib significantly inhibited tumor growth and prolonged remission
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