Inhibition of Akt and MAPK pathways elevated potential of TNFalpha in inducing apoptosis in ameloblastoma.
Tumor necrosis factor alpha (TNFalpha) can trigger both cell survival and apoptosis. In the present study, from the flow cytometry results, we found that the prolonged-treatment of TNFalpha 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 TNFalpha. Our further investigation using specific caspase inhibitors showed that caspase-3 played a crucial role in mediating TNFalpha-induced apoptosis in AM-1 cells. In addition, significant elevation of TNFalpha 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 TNFalpha in AM-1 cells. These results suggested that TNFalpha induced both cell survival and apoptosis pathways in ameloblastoma and potential of TNFalpha in inducing apoptosis can be improved by inhibiting TNFalpha-induced Akt and p44/42 mitogen-activated protein kinase (MAPK) cell survival pathways.
Sandra
Ferry
F
Section of Oral and Maxillofacial Oncology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ferry@dent.kyushu-u.ac.jp
Hendarmin
Laifa
L
Nakao
Yu
Y
Nakamura
Norifumi
N
Nakamura
Seiji
S
D000564:Ameloblastoma / Q000378:metabolism / Q000503:physiopathology*; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000494:pharmacology; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D007573:Jaw Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases