P53 is known as a transcription factor to control apoptotic cell death through regulating a series of target genes in nucleus[3]. Pifithrin-α hydrobromide is an inhibitor of p53; reversibly blocks p53-dependent transcriptional activation and apoptosis[4]. Pifithrin-α also acts as an aryl hydrocarbon receptor (AhR) agonist and. Pifithrin-α is a potent AhR agonist as determined by its ability to bind the AhR, induce formation of its DNA binding complex, activate reporter activity, and up-regulate the classic AhR target gene CYP1A1[5]. When the experiment is performed with Pifthirin-α (PFT-α) hydrobromide, a pharmacological p53 inhibitor, the percentage of annexin V-positive Foxe3-/- SMCs decreases to WT levels. Pifithrin-α (2.2 mg/kg, i.p.) significantly reduces the incidence of aortic rupture and intramural hematomas in Foxe3-/- mice that underwent transverse aortic constriction (TAC) (50% to 17%, P<0.05). After Pifthirin-α treatment, the mean diameter of the ascending aorta and the percentage of TUNEL-positive cells in the aortic media are also normalized to WT levels in surviving Foxe3-/- animals[6].
Pifithrin-α HBr 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293-OATP1B3 cells
30 µM
5 h
To investigate the effect of Pifithrin-α on microcystin-LR-induced cytotoxicity, results showed that Pifithrin-α concentration-dependently attenuated the susceptibility of HEK293-OATP1B3 cells to microcystin-LR.
Environ Health Perspect. 2010 Sep;118(9):1292-8.
Human Coronary Artery Smooth Muscle Cells (HCASMC)
10 μM
To investigate the effect of Pifithrin-α on the p53 signaling pathway in CDKN2B-deficient cells, results showed that Pifithrin-α inhibited the p53 signaling pathway and reduced apoptosis.
Inhibition of p53 activation, reduction of caspase-3 cleavage, and significant reduction of OH-ME-induced cell death
Cell Death Dis. 2022 Nov 29;13(11):1009.
HK2 cells
10μM
48 h
Inhibit p53 protein levels and activity, and evaluate its impact on TGFβ1 mRNA and protein levels as well as mesenchymal transition. The results showed that PFT-α treatment partially reversed the increases in TGFβ1 mRNA and protein levels, as well as the expression of mesenchymal markers α-SMA and Vimentin induced by Bmi1 knockdown or H2O2 treatment, while partially restoring the expression of the epithelial marker E-Cadherin.
Int J Biol Sci. 2024 Mar 11;20(6):2008-2026.
A172 cells
10 μM
Pifithrin-α (p53 inhibitor) was used to perform the rescue experiment, but the results indicated that pifithrin-α (PFT-a) could not significantly affect the impact of p62 overexpression on SLC7A11 in A172 (p53 wild-type) cells.
Cell Biosci. 2022 Feb 25;12(1):20.
Pifithrin-α HBr 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Piezo1scKO mouse model
Intraperitoneal injection
2 mg/kg
Every second day until sample isolation
Inhibition of P53 activity, reduction of senescent muscle stem cell formation, and improvement of muscle regeneration
Redox Biol. 2022 Jun;52:102309
Mice
Carotid Artery Ligation (CAL) model and Elastase-induced Abdominal Aortic Aneurysm (AAA) model
Intraperitoneal injection
2.2 mg/kg
Every 48 hours until sacrifice
To investigate the effect of Pifithrin-α on vascular remodeling and aneurysm formation in Cdkn2b-deficient mice, results showed that Pifithrin-α inhibited the p53 signaling pathway, reduced apoptosis, and reversed the vascular remodeling phenotype.
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