The flavouring phytochemical 2-pentanone reduces prostaglandin production and COX-2 expression in colon cancer cells.
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.
Pettersson
Jenny
J
Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
Karlsson
Pernilla Christina
PC
Göransson
Ulf
U
Rafter
Joseph James
JJ
Bohlin
Lars
L
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*
D052246:Cyclooxygenase 2 Inhibitors; D005421:Flavoring Agents; D010422:Pentanones; D051546:Cyclooxygenase 2; C076402:2-pentanone; D015232:Dinoprostone