title: Dioscorea japonica extract down-regulates prostaglandin E2 synthetic pathway and induces apoptosis in lung cancer cells.
abstract: Prostaglandin E2 plays a role in an array of pathophysiological responses, including inflammation, carcinogenesis and so on. Prostaglandin E2 is synthesized from arachidonic acid by the enzymes cyclooxygenase and prostaglandin E synthase. In some pathological conditions, the isozymes cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are transiently induced, leading to prostaglandin E2 overproduction. The present study showed that Dioscorea japonica extract suppresses mRNA expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in human non-small-cell lung carcinoma A549 cells in a dose-dependent manner. The suppressive effects of Dioscorea japonica extract on the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 were confirmed by Western blotting, cyclooxygenase activity and prostaglandin E2 production. Dioscorea japonica extract induced the translocation of nuclear factor-κB from the nucleus to the cytosol and inhibited the activity of the cyclooxygenase-2 promoter. Furthermore Dioscorea japonica extract suppressed the expression of the anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2 and enhanced apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive intensity in A549 cells. These results suggest that Dioscorea japonica extract suppresses the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, with the regulation of the transcriptional activity of cyclooxygenase-2, and induces apoptosis in cancer cells. Thus, Dioscorea japonica may contribute to the prevention of prostaglandin E2-mediated pathophysiological responses such as carcinogenesis and inflammation.
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Suzuki-Yamamoto
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Tsukayama
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Takafuji
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Takae
authors.initials: T
authors.lastname: Hanada
authors.affiliation: Department of Biochemistry, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Kimoto
authors.affiliation: Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Takahashi
keywords: Dioscorea japonica; apoptosis; cancer cells; cyclooxygenase-2; microsomal prostaglandin E synthase-1