Characterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines.

Hdl Handle:
http://hdl.handle.net/10147/209275
Title:
Characterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines.
Authors:
Alam, Mahmood; Wang, Jiang Huai; Coffey, John Calvin; Qadri, Syed Suhail; O'Donnell, Aonghus; Aherne, Thomas; Redmond, Henry Paul
Affiliation:
Department of Cardiothoracic Surgery, Cork University Hospital, Cork, Republic of, Ireland.
Citation:
Ann Surg Oncol. 2007 Sep;14(9):2678-84. Epub 2007 Jun 30.
Journal:
Annals of surgical oncology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209275
DOI:
10.1245/s10434-007-9359-y
PubMed ID:
17602268
Abstract:
BACKGROUND: Cyclooxygenase-2 enzyme (COX-2) is overexpressed in human non-small cell lung cancer (NSCLC) but is not expressed in small cell lung cancer. Selective COX-2 inhibitors have been shown to induce apoptosis in NSCLC cells, an effect which is associated with the regulation of intracellular MAP kinase (MAPK) signal pathways. Our aims were to characterize the effects of COX-2 inhibition by rofecoxib on apoptosis in human NSCLC and small cell lung cancer cell lines. METHODS: The human NSCLC cell line NCI-H2126 and small cell lung cancer cell line DMS-79 were used. Constitutive COX-2 protein levels were first determined by Western blot test. Levels of apoptosis were evaluated by using propidium iodide staining on FACScan analysis after incubation of NCI-H2126 and DMS-79 with p38 MAPK inhibitor SB202190 (25 ?microM), NF-kappaB inhibitor SN50 (75 microg/mL), and rofecoxib at 100 and 250 microM. All statistical analysis was performed by analysis of variance. RESULTS: Western blot test confirmed the presence of COX-2 enzyme in NCI-H2126 and absence in DMS-79. Interestingly, rofecoxib treatment demonstrated a dose-dependent increase in apoptosis in both cell lines. Given this finding, the effect of rofecoxib on NF-kappaB and p38 MAPK pathways was also examined. Apoptosis in both cell lines was unaltered by SN50, either alone or in combination with rofecoxib. A similar phenomenon was observed in NCI-H2126 cells treated with SB202190, either alone or in combination with rofecoxib. In contrast, p38 MAPK inhibition greatly upregulated DMS-79 apoptosis in a manner that was unaltered by the addition of rofecoxib. CONCLUSIONS: Rofecoxib led to a dose-dependent increase in apoptosis in both tumor cell lines. This effect occurred independently of COX-2, NF-kappaB, and p38 MAPK pathways in DMS-79 cells. As such, rofecoxib must act on alternative pathways to regulate apoptosis in human small cell lung cancer cells.
Language:
eng
MeSH:
Analysis of Variance; Apoptosis/*drug effects; Blotting, Western; Carcinoma, Non-Small-Cell Lung/*enzymology; Carcinoma, Small Cell/*enzymology; Dose-Response Relationship, Drug; Enzyme Inhibitors/pharmacology; Humans; Imidazoles/pharmacology; Lactones/*pharmacology; Lung Neoplasms/*enzymology; NF-kappa B/antagonists & inhibitors; Pyridines/pharmacology; Signal Transduction; Sulfones/*pharmacology; Tumor Cells, Cultured; Up-Regulation; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
ISSN:
1068-9265 (Print); 1068-9265 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorAlam, Mahmooden_GB
dc.contributor.authorWang, Jiang Huaien_GB
dc.contributor.authorCoffey, John Calvinen_GB
dc.contributor.authorQadri, Syed Suhailen_GB
dc.contributor.authorO'Donnell, Aonghusen_GB
dc.contributor.authorAherne, Thomasen_GB
dc.contributor.authorRedmond, Henry Paulen_GB
dc.date.accessioned2012-02-03T15:16:54Z-
dc.date.available2012-02-03T15:16:54Z-
dc.date.issued2012-02-03T15:16:54Z-
dc.identifier.citationAnn Surg Oncol. 2007 Sep;14(9):2678-84. Epub 2007 Jun 30.en_GB
dc.identifier.issn1068-9265 (Print)en_GB
dc.identifier.issn1068-9265 (Linking)en_GB
dc.identifier.pmid17602268en_GB
dc.identifier.doi10.1245/s10434-007-9359-yen_GB
dc.identifier.urihttp://hdl.handle.net/10147/209275-
dc.description.abstractBACKGROUND: Cyclooxygenase-2 enzyme (COX-2) is overexpressed in human non-small cell lung cancer (NSCLC) but is not expressed in small cell lung cancer. Selective COX-2 inhibitors have been shown to induce apoptosis in NSCLC cells, an effect which is associated with the regulation of intracellular MAP kinase (MAPK) signal pathways. Our aims were to characterize the effects of COX-2 inhibition by rofecoxib on apoptosis in human NSCLC and small cell lung cancer cell lines. METHODS: The human NSCLC cell line NCI-H2126 and small cell lung cancer cell line DMS-79 were used. Constitutive COX-2 protein levels were first determined by Western blot test. Levels of apoptosis were evaluated by using propidium iodide staining on FACScan analysis after incubation of NCI-H2126 and DMS-79 with p38 MAPK inhibitor SB202190 (25 ?microM), NF-kappaB inhibitor SN50 (75 microg/mL), and rofecoxib at 100 and 250 microM. All statistical analysis was performed by analysis of variance. RESULTS: Western blot test confirmed the presence of COX-2 enzyme in NCI-H2126 and absence in DMS-79. Interestingly, rofecoxib treatment demonstrated a dose-dependent increase in apoptosis in both cell lines. Given this finding, the effect of rofecoxib on NF-kappaB and p38 MAPK pathways was also examined. Apoptosis in both cell lines was unaltered by SN50, either alone or in combination with rofecoxib. A similar phenomenon was observed in NCI-H2126 cells treated with SB202190, either alone or in combination with rofecoxib. In contrast, p38 MAPK inhibition greatly upregulated DMS-79 apoptosis in a manner that was unaltered by the addition of rofecoxib. CONCLUSIONS: Rofecoxib led to a dose-dependent increase in apoptosis in both tumor cell lines. This effect occurred independently of COX-2, NF-kappaB, and p38 MAPK pathways in DMS-79 cells. As such, rofecoxib must act on alternative pathways to regulate apoptosis in human small cell lung cancer cells.en_GB
dc.language.isoengen_GB
dc.subject.meshAnalysis of Varianceen_GB
dc.subject.meshApoptosis/*drug effectsen_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshCarcinoma, Non-Small-Cell Lung/*enzymologyen_GB
dc.subject.meshCarcinoma, Small Cell/*enzymologyen_GB
dc.subject.meshDose-Response Relationship, Drugen_GB
dc.subject.meshEnzyme Inhibitors/pharmacologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImidazoles/pharmacologyen_GB
dc.subject.meshLactones/*pharmacologyen_GB
dc.subject.meshLung Neoplasms/*enzymologyen_GB
dc.subject.meshNF-kappa B/antagonists & inhibitorsen_GB
dc.subject.meshPyridines/pharmacologyen_GB
dc.subject.meshSignal Transductionen_GB
dc.subject.meshSulfones/*pharmacologyen_GB
dc.subject.meshTumor Cells, Cultureden_GB
dc.subject.meshUp-Regulationen_GB
dc.subject.meshp38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsen_GB
dc.titleCharacterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines.en_GB
dc.contributor.departmentDepartment of Cardiothoracic Surgery, Cork University Hospital, Cork, Republic of, Ireland.en_GB
dc.identifier.journalAnnals of surgical oncologyen_GB
dc.description.provinceMunster-

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