In the United States, the primary cancer in elderly men is prostate cancer (33% of newly diagnosed malignancies), but the prevalence is 75% lower in some Mediterranean countries. A possible explanation for the large difference in prostate cancer cases is that in Mediterranean countries the diet includes fish, olive oil and high amounts of nuts, fruits, vegetables, along with a regular intake of wine with meals several times per week. The LNCaP prostate cancer cells represent the nonaggressive androgen-dependent cell model that expresses moderate levels of cyclooxygenase-2 (COX-2). Epidemiological evidence indicates that polyphenolic compounds in diets are protective against cancer, and cyanidin and kaempferol are abundant in wine and plants. Therefore, the objective of the investigation was to determine the effects of cyanidin and kaempferol on prostaglandin E2 (PGE2) and COX-2 protein levels, and if peroxisome proliferator-activated receptor gamma (PPARgamma) and nuclear factor kappaB (NFkappaB) are involved in the expression of COX-2 in prostate cancer cells. Cyanidin and kaempferol at 1 microM reduced the level of PGE2 in LNCaP cell cultures and also attenuated the effect of arachidonic acid on increasing the amount of PGE2. Cyanidin reduced the levels of COX-2 protein in a dose- and time-dependent fashion. PPARgamma mRNA levels were lower in cells treated after 24 h with kaempferol (0.1 and 1 microM) and cyanidin (1 microM). The reduction of COX-2 mRNA by kaempferol and cyanidin may be mediated through the actions of NFkappaB and PPARgamma as nuclear factors that bind to the COX-2 gene promoter.