Hot shock protein 70(HSP70) is an ATP-dependent chaperone that can be induced by cellular stress and its aberrant activation is commonly observed in various malignancies. Pifithrin-μ is an inhibitor of inducible HSP70. It strongly inhibited cell viability with IC50 values of 2.5, 6.1, 4.4, 6.1, 12.7, 8.4 and 11.2 μM in NALM-6, TOM-1, BE-13, Jurkat, KG-1a, K562 and K562-r cells, respectively. In NALM-6 and KG-1a cell lines, incubation with Pifithrin-μ (4 and 5 μM for NALM-6; 40 and 60 μM for KG-1a) for 24h caused a remarkably reduced proportion of cells in S phase. Around 22% of NALM-6 cells were observed in the sub-G0/1 fraction after incubation with 5μM Pifithrin-μ, while only 2% of KG-1a cells were within this fraction after 60 μM Pifithrin-μ treatment. Incubation of NALM-6 cells with Pifithrin-μ at 4, 5 and 6.5 μM resulted in 34, 59 and 80% apoptotic cells above spontaneous apoptosis, respectively. Moreover, the intracellular AKT and ERK1/2 levels in NALM-6 cells was decreased by 10-h incubation of 10μM Pifithrin-μ[3]. In nude mice inoculated with human pancreatic cancer MiaPaca-2 cells, intraperitoneal injection with Pifithrin-μ (25mg/kg, 100μL) significantly enhanced the inhibitory effect of TRAIL on MiaPaca-2 tumor growth[4].
Pifithrin-μ 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
human T293 cells
15 μM
Function assay
48 h
Binding affinity to p53 transfected in human T293 cells assessed as reduction in p53 bound-Bcl-2 at 15 uM after 48 hrs
16862141
Saos-2 cells
10 μM
Function assay
48 h
Binding affinity to p53 transfected in human Saos-2 cells harboring pLV-53 assessed as reduction of p53 protein in mitochondria at 10 uM after 48 hrs
16862141
WI38 cells
10 μM
Function assay
24 h
Inhibition of p53-mediated apoptosis in human WI38 cells assessed as cell survival at 10 uM after 24 hrs by methylene blue assay
16862141
Pifithrin-μ 动物研究
Dose
Mice: 1 mg/kg or 5 mg/kg[3] (i.p.), 40 mg/kg[2] (i.p.)
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