title: The flavouring phytochemical 2-pentanone reduces prostaglandin production and COX-2 expression in colon cancer cells.
abstract: Many phytochemicals found in the diet may prevent colon carcinogenesis by affecting biochemical processes in the colonic mucosa. Inflammation and subsequent elevation of the enzyme cyclooxygenase-2 (COX-2) are two such factors involved in the development of colon cancer, and inhibition of these processes could be important targets for chemoprevention. We have previously shown COX-2 inhibitory activity locally in the colon; e.g. in human fecal water from a group of vegetarians. In this study we focus on 2-pentanone, a frequently occurring compound in common foods such as banana and carrot. The aim was to study the inhibitory effects on prostaglandin production and COX-2 protein expression in tumour necrosis factor-alpha stimulated colon cancer cells (HT29) by radioimmunoassay and Western blotting. 2-Pentanone inhibited both prostaglandin production and COX-2 protein expression in human colon cancer cells. A concentration of 400 mumol/l 2-pentanone inhibited the prostaglandin production by 56.9+/-12.9% which is in the same range as the reference compound NS398 (59.8+/-7.6%). The two highest concentrations of 2-pentanone were further analyzed by Western blot, and 400 micromol/l and 200 micromol/l 2-pentanone resulted in a 53.3+/-9.6% and +/-27.1% reduction of the COX-2 protein levels respectively. Further studies on flavouring compounds, for example 2-pentanone, as colon cancer chemopreventives would be very valuable, and such results may contribute to future dietary recommendations.
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Pettersson
authors.forename: Pernilla Christina
authors.initials: PC
authors.lastname: Karlsson
authors.forename: Ulf
authors.initials: U
authors.lastname: Göransson
authors.forename: Joseph James
authors.initials: JJ
authors.lastname: Rafter
authors.forename: Lars
authors.initials: L
authors.lastname: Bohlin
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D014676:Diet, Vegetarian; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005421:Flavoring Agents / Q000494:pharmacology*; D006801:Humans; D010422:Pentanones / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005421:Flavoring Agents; D010422:Pentanones; D051546:Cyclooxygenase 2; C076402:2-pentanone; D015232:Dinoprostone