The small ubiquitin-like modifier (SUMO) modification, also called sumoylation, is a posttranslational modification of protein substrates, which is essential in cellular stress response. 2',3',4'-Trihydroxyflavone (2-D08) is a synthetic oxygenated flavonoid that inhibits sumoylation with an IC50 of 6 μM. The treatment of 2-D08 for 90 min in vitro inhibited the conjugation of SUMO-1, SUMO-2, and SUMO-3 to IκBα dose-dependently from 1 - 30 μM. The incubation of 30 μM 2-D08 for 6 hours inhibited the sumoylation of topoisomerase-I in BT-474 breast cancer cell lines. A significant overall inhibition of fibril formation was observed in the presence of 100μM 2-D08 at 48 hours. The incubation of 0.1 – 2 μM Aβ1 - 42Myc lymphoma cells 48 hour after the exposure, followed by rapid growth arrest and apoptotic cell death. When incubated with 75 μM 2-D08 for 24 hours, the fold change of the sub-G1 fraction in P493-6 lymphoma cells treated without tetracycline (Myc-off) were significantly lower than that in cells treated with tetracycline (Myc-on).
作用机制
2',3',4'-Trihydroxyflavone inhibits protein sumoylation by preventing transfer of SUMO from the UBC9-SUMO thioester to the substrate.
2-D08 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT116 cells
200 µM
24 hours
The combination of 2-D08 with etoposide significantly enhanced apoptosis in HCT116 cells.
Signal Transduct Target Ther. 2020 Jun 24;5(1):80.
2-D08 inhibited cell viability in a dose- and time-dependent manner and significantly inhibited the colony-forming ability of SK-LMS-1 cells.
Oncol Rep. 2024 Jul;52(1):97.
SK-UT-1B cells
0-100 µM
24 or 48 hours
2-D08 slightly increased the apoptotic rate in SK-UT-1B cells but did not affect cell cycle progression.
Oncol Rep. 2024 Jul;52(1):97.
16HBE cells
30 µM
6 hours
To investigate the effect of 2-D08 on IL-13-induced ROCK2 phosphorylation, results showed that 2-D08 significantly reduced IL-13-induced ROCK2 phosphorylation
Nat Commun. 2023 Jul 1;14(1):3887.
UACC-1598DM cells
30 µM
7 days
Reduced SUMO1/2 expression, decreased DM counts, and lowered expression of DM-carried genes
Cancer Biol Ther. 2024 Dec 31;25(1):2323768.
Colo320DM cells
30 µM
Decreased DM counts and lowered expression of DM-carried genes
Cancer Biol Ther. 2024 Dec 31;25(1):2323768.
2-D08 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SCID female mice
UACC-1598DM xenograft model
IntratumOral injection
10 mg/kg
Every other day for 10 days
Reduced tumor growth rate, decreased DM counts, and lowered expression of DM-carried genes
2 hours after each OVA or HDM atomization, once daily for 7 days
To investigate the effect of 2-D08 on allergic airway inflammation and goblet cell metaplasia, results showed that 2-D08 significantly attenuated OVA- or HDM-induced airway inflammation, hyperreactivity, and goblet cell metaplasia
Nat Commun. 2023 Jul 1;14(1):3887.
Rats
Spared Nerve Injury model
Intrathecal injection
10, 30, 60, or 100 μM
Once daily for 5 days
2-D08 significantly decreased the upregulation of UBC9 protein and SUMOylated Kir7.1 induced by SNI and increased the surface accumulation of Kir7.1 in the spinal cord.
CNS Neurosci Ther. 2022 Aug;28(8):1259-1267
Nude mice
HCT116 xenograft model
Intraperitoneal injection
5 mg/kg
Every 2 days for 10 days
The combination of 2-D08 with etoposide significantly inhibited tumor growth.
Signal Transduct Target Ther. 2020 Jun 24;5(1):80.
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