Inauhzin at a concentration of 10 µM elevates p53 levels comparably to actinomycin D at 10 nM and promotes p53-dependent cytotoxicity via its distinct functional groups in human lung carcinoma H460 cells. A lower concentration of Inauhzin (2 µM) enhances both the level and activity of p53, along with initiating p53-dependent apoptosis. It stabilizes p53, prevents its ubiquitylation, and increases p53 acetylation in H460 cells, specifically without affecting tubulin. This acetylation is impacted by the knockdown of SIRT1[1]. At doses up to 2 µM, Inauhzin markedly boosts the expression and activity of p53 in both HCT116p53+/+ and H460 cells in a dose-responsive manner. When combined with Nutlin-3, Inauhzin displays synergistic cytotoxic effects, particularly in cells with low sensitivity to Nutlin-3, and jointly they trigger p53-dependent apoptosis[2].
体内研究
Administered intraperitoneally at 30 mg/kg, Inauhzin significantly initiates apoptosis and reduces tumor growth in H460 xenografts harboring p53[1].
At the same dosage, Inauhzin reduces the tumor volume of HCT116 by about 70%. When used alongside 150 mg/kg Nutlin-3 at 15 mg/kg, Inauhzin shows significant synergy in inducing p53, apoptosis, and tumor suppression in HCT116p53+/+ xenografts[2].
体外研究
Inauhzin at a concentration of 10 µM elevates p53 levels comparably to actinomycin D at 10 nM and promotes p53-dependent cytotoxicity via its distinct functional groups in human lung carcinoma H460 cells. A lower concentration of Inauhzin (2 µM) enhances both the level and activity of p53, along with initiating p53-dependent apoptosis. It stabilizes p53, prevents its ubiquitylation, and increases p53 acetylation in H460 cells, specifically without affecting tubulin. This acetylation is impacted by the knockdown of SIRT1[1].
At doses up to 2 µM, Inauhzin markedly boosts the expression and activity of p53 in both HCT116p53+/+ and H460 cells in a dose-responsive manner. When combined with Nutlin-3, Inauhzin displays synergistic cytotoxic effects, particularly in cells with low sensitivity to Nutlin-3, and jointly they trigger p53-dependent apoptosis[2].
Inauhzin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT116 cells
2 µM
6 hours
Induced p53 levels and activity
EMBO Mol Med. 2012 Apr;4(4):298-312.
H1299 cells
2 µM
24 hours
INZ(c) treatment decreased c-Myc mRNA and protein levels.
Cancer Biol Ther. 2015;16(3):412-9.
A549 cells
0.5 µM
18 hours
Induced p53 levels and activity
EMBO Mol Med. 2012 Apr;4(4):298-312.
H460 cells
10 µM
18 hours
Induced p53 levels
EMBO Mol Med. 2012 Apr;4(4):298-312.
A549
0.5 µM
18 hours
Combined treatment of INZ and DOX significantly induced the level of p53, p21, and cleaved PARP
Neoplasia. 2013 May;15(5):523-34.
HCT116p53+/+
0.5 µM
18 hours
Combined treatment of INZ and CIS or DOX significantly induced the level of p53, p21, and cleaved PARP
Neoplasia. 2013 May;15(5):523-34.
H460
0.5 µM
18 hours
Combined treatment of INZ and CIS or DOX significantly induced the level of p53, p21, and cleaved PARP
Neoplasia. 2013 May;15(5):523-34.
A549 cells
1 µM
18 hours
To test the effect of Inauhzin alone or in combination with Nutlin-3 on p53 levels and activity. Results showed that the combination of Inauhzin and Nutlin-3 significantly increased the levels of p53 and its target proteins p21 and cleaved PARP.
Cancer Biol Ther. 2012 Aug;13(10):915-24.
H460 cells
1 µM
18 hours
To test the effect of Inauhzin alone or in combination with Nutlin-3 on p53 levels and activity. Results showed that the combination of Inauhzin and Nutlin-3 significantly increased the levels of p53 and its target proteins p21 and cleaved PARP.
Cancer Biol Ther. 2012 Aug;13(10):915-24.
HCT116 p53+/+ cells
0.5 µM and 1 µM
18 hours
To test the effect of Inauhzin alone or in combination with Nutlin-3 on p53 levels and activity. Results showed that Inauhzin alone or in combination with Nutlin-3 significantly increased the levels of p53 and its target proteins p21, PUMA, and cleaved PARP.
Cancer Biol Ther. 2012 Aug;13(10):915-24.
HCT116 p53+/+ and HCT116 p53−/− cells
4 µM
18 hours
Microarray analysis identified TFIIS.h as a potential p53 target gene, induced by INZ only in HCT116 p53+/+ cells.
Sci Rep. 2016 Mar 23;6:23542.
Vero E6 cells
12.96 µM (EC50)
22 hours
To evaluate the inhibitory effect of Inauhzin on SARS-CoV-2 replication, results showed antiviral activity in the cell-based model with an EC50 of 12.96 μM.
Biochem J. 2021 Jul 16;478(13):2481-2497.
Raji cells
0, 0.63, or 2.5 µM
24 hours
INZ(c) significantly inhibited cell proliferation and viability.
Cancer Biol Ther. 2015;16(3):412-9.
Inauhzin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c nude mice
HCT116 subcutaneous xenograft model
Oral gavage
15 mg/kg and 30 mg/kg
Every 2 days for 14 days
To evaluate the inhibitory effect of Inauhzin on the growth of HCT116 xenografts. Results showed that Inauhzin significantly suppressed tumor volume and weight, induced apoptosis in tumor tissues, and had no significant toxic effects on body weight and major organs.
Redox Biol. 2022 Jul;53:102334
SCID mice
HCT116 p53+/+ xenograft tumor model
Intraperitoneal injection for Inauhzin, oral administration for Nutlin-3
15 mg/kg Inauhzin + 150 mg/kg Nutlin-3
Inauhzin once daily, Nutlin-3 twice daily for 4 days followed by 2 days off, for 21 days
To test the inhibitory effect of Inauhzin and Nutlin-3 combination on xenograft tumor growth. Results showed that the combination significantly reduced tumor volume and weight, and increased the levels of p53 and its target proteins.
Cancer Biol Ther. 2012 Aug;13(10):915-24.
SCID mice
H460 xenograft tumor model
Intraperitoneal injection
20 mg/kg
INZ once per day for 21 days; CIS once per week for 3 weeks
Combined treatment of INZ and CIS significantly suppressed tumor growth, reducing tumor volume and weight
搜索
