Inhibition of Akt and MAPK pathways elevated potential of TNFα in inducing apoptosis in ameloblastoma

SummaryTumor necrosis factor alpha (TNFα) can trigger both cell survival and apoptosis. In the present study, from the flow cytometry results, we found that the prolonged-treatment of TNFα until 24 h, resulted apoptosis in AM-1 cells (ameloblastoma cell line). These results were confirmed by DAPI staining, which showed nuclear fragmentation feature of AM-1 cells under treatment of TNFα. Our further investigation using specific caspase inhibitors showed that caspase-3 played a crucial role in mediating TNFα-induced apoptosis in AM-1 cells. In addition, significant elevation of TNFα potential in inducing apoptosis was seen by applying LY294002, phosphatidylinositol-3-OH kinase (PI3K) inhibitor, or U0126, mitogen-activated extracellular-regulated kinase (MEK1/2) inhibitor, prior to the treatment of TNFα in AM-1 cells. These results suggested that TNFα induced both cell survival and apoptosis pathways in ameloblastoma and potential of TNFα in inducing apoptosis can be improved by inhibiting TNFα-induced Akt and p44/42 mitogen-activated protein kinase (MAPK) cell survival pathways.