Induction of apoptosis by dopamine in human oral tumor cell lines.
Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.
Terasaka
H
H
Department of Oral Diagnosis, Meikai University School of Dentistry, Saitama, Japan.
Tamura
A
A
Takayama
F
F
Kashimata
M
M
Ohtomo
K
K
Machino
M
M
Fujisawa
S
S
Toguchi
M
M
Kanda
Y
Y
Kunii
S
S
Kusama
K
K
Ishino
A
A
Watanabe
S
S
Satoh
K
K
Takano
H
H
Takahama
M
M
Sakagami
H
H
D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053938:DNA Fragmentation; D004298:Dopamine / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005707:Gallic Acid / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007633:Keratins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D009363:Neoplasm Proteins; D011725:Pyridines; D003035:Cobalt; D005707:Gallic Acid; D007633:Keratins; D006861:Hydrogen Peroxide; D002374:Catalase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003546:Cysteine Endopeptidases; C018021:cobaltous chloride; C093642:SB 203580; D001205:Ascorbic Acid; D004298:Dopamine