title: Inhibition of Akt and MAPK pathways elevated potential of TNFalpha in inducing apoptosis in ameloblastoma.
abstract: 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.
authors.affiliation: 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
authors.forename: Ferry
authors.initials: F
authors.lastname: Sandra
authors.forename: Laifa
authors.initials: L
authors.lastname: Hendarmin
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakao
authors.forename: Norifumi
authors.initials: N
authors.lastname: Nakamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: 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*
chemical_list: 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