Abstract
Background:
Licofelone, a potent antiinflammatory agent has been reported to interfere with the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) signaling pathways with few side-effects. However, the underlying mechanism of licofelone against human cancer is not understood.
Materials and methods:
Human and mouse prostate cancer cells were exposed to licofelone in a time- and dose-dependent manner. Cell growth/cell viability, apoptosis, and expression of COX-2 and 5-LOX at the gene and protein levels were investigated.
Results:
For the first time, it was demonstrated that licofelone inhibited prostate cancer cell growth and significantly down-regulated COX-2 and 5-LOX expression. A weak inhibitory effect on COX-1 protein was also observed.
Conclusion:
Licofelone inhibited COX-2 and 5-LOX simultaneously and prevented overall cancer cell growth by enhancing apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Validating the dual role of licofelone in animal models of prostate cancer is critical for promoting its use as a potential chemopreventive or therapeutic agent.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acetates / pharmacology*
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / enzymology
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Arachidonate 5-Lipoxygenase / biosynthesis
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Arachidonate 5-Lipoxygenase / genetics
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Cell Growth Processes / drug effects
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Cyclooxygenase 2 / biosynthesis
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / pharmacology
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Dose-Response Relationship, Drug
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Humans
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Lipoxygenase Inhibitors
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Male
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Mice
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Mice, Transgenic
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / enzymology
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / pathology
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Pyrroles / pharmacology*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Transcription, Genetic / drug effects
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / genetics
Substances
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Acetates
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Antineoplastic Agents
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Cyclooxygenase 2 Inhibitors
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Lipoxygenase Inhibitors
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Pyrroles
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Arachidonate 5-Lipoxygenase
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Cyclooxygenase 2
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licofelone