BACKGROUND AND OBJECTIVES: In oral cavity cancer (OCC) cells, the effects of interleukin-4 (IL-4) are various according to the cell specificity. However, if IL-4 induces apoptosis on OCC cells, the mediator of this apoptosis is uncertain. Therefore, we investigated whether apoptosis of OCC cells occurs by IL-4 and whether 15-lipoxygenase-1 (15-LO-1) induced by IL-4 is the possible mediator of this apoptosis. MATERIALS AND METHODS: SCC 1483 cells were used. Flow cytometry and poly ADP-ribose polymerase cleavage were used to examine apoptosis. Western blot analysis and reverse transcription-polymerase chain reaction were used to measure 15-LO-1 protein and mRNA. RESULTS: The inhibition of cell proliferation by more than 50% was noted from 10 ng/ml of IL-4. At this dose, apoptosis was observed and this apoptosis was inhibited by 2.2 microM caffeic acid. 15-LO-1 expression was observed from the 8 hour treatment of IL-4 and apoptosis increased after the 24 hour treatment of IL-4. In this apoptosis, caspase cascade, cyclooxygenase-2, and non-steroidal anti-inflammatory drugs-activated gene-1 (NAG-1) were not involved. CONCLUSION: IL-4 induced apoptosis in SCC 1483 OCC cells and 15-LO-1 induced by IL-4 may mediate this apoptotic pathway.
Adenosine Diphosphate Ribose ; Apoptosis* ; Arachidonate 15-Lipoxygenase ; Blotting, Western ; Cell Proliferation ; Cyclooxygenase 2 ; Flow Cytometry ; Interleukin-4* ; Mouth Neoplasms ; Mouth* ; RNA, Messenger ; Sensitivity and Specificity

BACKGROUND AND OBJECTIVES: The purpose of this study is to investigate whether Ginkgo biloba extract (EGb 761) can suppress IL-1beta-induced MUC5AC gene expression in NCI-H292 human airway epithelial cells and to discover what its possible mechanism is. MATERIALS AND METHODS: NCI-H292 human pulmonary mucoepidermoid carcinoma cell line was used. MUC5AC mRNA and protein were measured using the RT-PCR and Western blot analysis. The activation of mitogen activated protein kinases (MAPKs) were determined by means of the Western blot analysis. RESULTS: MUC5AC was induced by treating the NCI-H292 cells with 10 ng/ml of IL-1beta for 24 hours. A pre-treatment of 200 microgram/ml of EGb 761 significantly suppressed the IL-1beta induced MUC5AC expression. The inhibition of MUC5AC gene expression by EGb 761 was noted to be suppressed via both the extracellular signal-regulated kinase (ERK) and the p38 MAPK pathways in a kinase-specific inhibitor study. CONCLUSION: EGb 761 suppresses IL-1beta-induced MUC5AC gene expression in the human airway epithelial cells. Therefore, it may be considered as a possible anti-hypersecretory agent.
Blotting, Western ; Carcinoma, Mucoepidermoid ; Cell Line ; Epithelial Cells* ; Gene Expression* ; Ginkgo biloba* ; Humans* ; Interleukin-1beta ; Mitogen-Activated Protein Kinases ; Mucins ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; RNA, Messenger

BACKGROUND AND OBJECTIVES: According to our previous study Ginkgo biloba extract (EGb 761) induces inhibition of cell proliferation and apoptosis in SCC 1483 oral cavity cancer cells. On the other hand, in lipopolysaccharide-stimulated RAW 264.7 cells, activation of mitogen activated protein kinase (MAPK) is the key event in the inhibition of inflammation by EGb 761. Therefore, we have investigated whether MAPK pathway is involved in the apoptotic process by EGb 761 in oral cavity cancer cell lines or not. SUBJECTS AND METHOD: In SCC 1483 oral cavity cancer cell lines, Western blot analysis, Fluorescence-activated cell sorter (FACS) analysis, and transient transfection using MAPK-dominant negative constructs were used. RESULTS: When SCC 1483 oral cavity cancer cell lines were treated with the concentration of 250 microgram/ml EGb 761, activation of extracellular signal-regulated kinase (ERK) and apoptosis were noted. This apoptosis was inhibited by the treatment with ERK inhibitor (PD 98059). In the transiently transfected cells by MAPK/ERK kinase 1 (MEK1)-dominant negative construct, phosphorylations of ERK and p90 ribosomal S 6 protein kinase (RSK1) were inhibited which led to the inhibition of apoptosis by EGb 761. The inhibition of apoptosis was also noted in the transfected cells by RSK1 dominant negative construct and cAMP response element binding protein (CREB)-dominant negative construct. CONCLUSION: In conclusion, the apoptosis of SCC 1483 oral cavity cancer cell lines by EGb 761 is linked to the activation of ERK and it can happen via ERK MAPK/RSK1/CREB signal transduction pathway.
Apoptosis* ; Blotting, Western ; Cell Line* ; Cell Proliferation ; Cyclic AMP Response Element-Binding Protein ; Ginkgo biloba* ; Hand ; Inflammation ; Mouth Neoplasms ; Mouth* ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Signal Transduction ; Transfection