title: Levamisole modulates prostaglandin E2 production and cyclooxygenase II gene expression in human colonic cancer cells.
abstract: BACKGROUND
  Colorectal adenocarcinoma is one of the leading causes of cancer mortality in the world. Recent studies have demonstrated that prostaglandin E(2) (PGE(2)) and cyclooxygenase (COX) are involved in the early development of colorectal cancer. Levamisole together with 5-fluorouracil has been shown to improve the survival of patients with Duke's C colon cancer. This study examined the effect of levamisole on PGE(2) production and COX-2 gene activation in immortalized human colon cells.
  
  
  METHODS
  Colon 205 cells, a human colonic cancer cell line, were exposed to Escherichia coli LPS (1 microg/mL) in the presence of levamisole (1 microm to 1 mm). The PGE(2) production was determined by enzyme-linked immunosorbent assay. In addition, cyclooxygenase II (COX-2) mRNA expression and COX-2 protein were measured by the real-time reverse transcription polymerase chain reaction and Western blot assay, respectively. Transcription factor nuclear factor (NF)-kappaB activity of the nuclear and cytoplasmic proteins was determined by Western blot assay with a P65 antibody.
  
  
  RESULTS
  Colon 205 cells produced significantly more PGE(2) when stimulated by LPS. Levamisole inhibited PGE(2) production by LPS-stimulated colon 205 cells in a dose-dependent fashion. In addition, COX-2 mRNA expression and COX-2 protein induced by LPS were also reduced by levamisole. Finally, NF-kappaB activation of LPS-stimulated colon cells was inhibited by levamisole.
  
  
  CONCLUSIONS
  Levamisole inhibits PGE(2) production by LPS-stimulated colon 205 cells. The inhibition of levamisole occurs at the transcription level of COX-2 gene and is regulated through NF-kappaB activation.
authors.affiliation: Department of Education and Research, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500 Taiwan.
authors.forename: Chin-Yen
authors.initials: CY
authors.lastname: Liu
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lai
authors.forename: Chong-Jeh
authors.initials: CJ
authors.lastname: Lo
mesh_terms: D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D007978:Levamisole / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D011448:Prostaglandin Antagonists; D012333:RNA, Messenger; D007978:Levamisole; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone