体外研究
SKA-31 activates KCa2/3 channels more potently than PK 26124, and is more selective over other Ion channels.
SKA-31 reduces cell viability with IC
50s
of 5.3 μM , 46.9 μM in HCT-116 cells and HCT-8 cells, respectively.
SKA-31 (5.3 μM; 0-96 hours) reduces HCT-116 cells proliferation when added at time zero at 5.3 μM.
SKA-31 triggers apoptosis in HCT-116 cells at 5 μM, and the effect is smaller in HCT-8 cells at 45 μM.
SKA-31 increases the percentage of cells in G0/G1 phase in HCT-116 and HCT-8 cell lines at 5 μM and 45 μM, respectively.
SKA-31 further activates Caspase 3 and reduces Akt phosphorylation induced by CDDP.
SKA-31 has a synergic effect with CDDP also on the inhibition of HCT-116 cell proliferation.
Cell Viability Assay
Cell Line:
HCT-116 cells, HCT-8 cells
Concentration:
Incubation Time:
24 hours
Result:
Reduced cell viability with IC
50s
of 5.3 μM , 46.9 μM in HCT-116 and HCT-8, respectively.
Cell Proliferation Assay
Cell Line:
HCT-116 cells
Concentration:
5.3 μM
Incubation Time:
0-96 hours
Result:
Reduced HCT-116 cells proliferation when added at time zero at IC
50S
value.
Apoptosis Analysis
Cell Line:
HCT-116 cells, HCT-8 cells
Concentration:
5 μM (HCT-116 cells), 45 μM (HCT-8 cells)
Incubation Time:
24 hours
Result:
Triggered apoptosis in HCT-116 cells, and the effect was smaller in HCT-8 cells.
Cell Cycle Analysis
Cell Line:
HCT-116 cells, HCT-8 cells
Concentration:
5 μM (HCT-116), 45 μM (HCT-8)
Incubation Time:
24 hours
Result:
Increased the percentage of cells in G0/G1 phase in HCT-116 and HCT-8 cell lines.
Western Blot Analysis
Cell Line:
HCT-116 cells
Concentration:
Incubation Time:
24 hours
Result:
Further activated Caspase 3 and reduced Akt phosphorylation when co-treatment with CDDP in HCT-116 cells.
体内研究
SKA-31 is not acutely toxic and has good pharmacokinetic properties.
SKA-31 potentiates native KCa3.1 and KCa2.3 in murine carotid endothelium with EC
50
values of 225 nM and 1.6 μM for KCa3.1 and KCa2.3, respectively.
SKA-31 stimulates KCa3.1 and KCa2.3 in vascular endothelial cells and increases acetylcholine-induced endothelium-derived hyperpolarizing factor (EDHF) -mediated vasodilation.
SKA-31 potentiates EDHF-type vasodilations and lowers blood pressure in mice. Injections of SKA-31 (1-30 mg/kg; i.p.) lower MAP over 24 hours in normotensive wild-type mice but not in KCa3.1(-/-) mice (-/-).
Animal Model:
16-25 weeks mice
Dosage:
1 mg/kg, 10 mg/kg, and 30 mg/kg
Administration:
Intraperitoneal injection
Result:
Lower MAP over 24 hours in normotensive wild-type mice but not in KCa3.1(-/-) mice (-/-).
