Abstract
Cigarette smoking, cyclooxygenase-2 (COX-2) and macrophages are independently associated with colorectal cancer. In the present study, cigarette smoke ethanol extract was applied to colon cancer cells (SW1116) or indirectly via activated macrophages (THP-1 cells) to attest their effects on cancer cell proliferation and tumor growth both in vitro and in vivo. Ethanol extract induced COX-2 expression in SW1116 and THP-1 cells. Combination of THP-1 pre-incubated medium and ethanol extract further potentiated COX-2 expression and proliferation of SW1116 cells. Tumor growth in nude mice was positively associated with the medium and/or ethanol extract treatments, together with the up-regulation of cell proliferation and angiogenesis, and down-regulation of apoptosis. Application of a COX-2 inhibitor (SC236) reduced tumor growth as well as cell proliferation and angiogenesis. These actions are partially depended on the decrease of COX-2 expression. Taken together, inhibition of COX-2 activity may have significant implication to prevent colon cancer in smokers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Cell Line
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Colonic Neoplasms / blood supply
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / pathology
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Complex Mixtures / chemistry
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Complex Mixtures / pharmacology*
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Cyclooxygenase Inhibitors / therapeutic use
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Dose-Response Relationship, Drug
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Ethanol / chemistry
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Humans
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Macrophages / drug effects*
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Macrophages / enzymology
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Membrane Proteins
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Mice
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Mice, Nude
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Neovascularization, Pathologic / prevention & control
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Nicotiana*
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Pyrazoles / pharmacology
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Pyrazoles / therapeutic use
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Smoke*
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use
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Thymidine / metabolism
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Time Factors
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Tritium
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Vascular Endothelial Growth Factor A / metabolism
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Xenograft Model Antitumor Assays / methods
Substances
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4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
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Complex Mixtures
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Membrane Proteins
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Proto-Oncogene Proteins c-bcl-2
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Pyrazoles
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Smoke
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Sulfonamides
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Vascular Endothelial Growth Factor A
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Tritium
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Ethanol
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Thymidine