Effect of dietary conjugated linoleic acid on phorbol ester-induced PGE2 production and hyperplasia in mouse epidermis.
Conjugated linoleic acid (CLA) is a chemoprotective fatty acid that inhibits phorbol ester-induced skin tumor promotion in mice. The goal of the present study was to determine potential chemoprotective mechanisms through which CLA may be acting. Mice were fed diets containing 0.0%, 0.5%, 1.0%, or 1.5% CLA (by wt) for six weeks. The epidermis was evaluated for fatty acid composition, vascular permeability, prostaglandin E2 (PGE2) production, hyperplasia, ornithine decarboxylase activity, and c-myc mRNA accumulation. Fatty acid analysis of mouse epidermis demonstrated a dose-dependent increase of CLA incorporation into phospholipids and neutral lipids. In mice topically treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), dietary CLA (1.5%) significantly (p < 0.05) reduced PGE2 synthesis (2-fold). Additionally, CLA lowered accumulation of c-myc mRNA, a gene commonly associated with regulating cell cycle components involved in cellular proliferation, although this trend was not significant. Vascular permeability was unaffected by dietary CLA. These data suggest that dietary CLA modulates TPA-induced tumor promotion through a mechanism involving PGE2 production; however, dietary CLA had a moderate effect on c-myc mRNA levels and little effect on TPA-induced hyperplasia and ornithine decarboxylase activity.
Kavanaugh
C J
CJ
Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907, USA.
Liu
K L
KL
Belury
M A
MA
D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D017931:DNA Primers; D004041:Dietary Fats / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016259:Genes, myc; D006965:Hyperplasia; D019787:Linoleic Acid / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate
D016588:Anticarcinogenic Agents; D017931:DNA Primers; D004041:Dietary Fats; D012333:RNA, Messenger; D019787:Linoleic Acid; D009955:Ornithine Decarboxylase; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate