title: Involvement of NADPH oxidases in suppression of cyclooxygenase-2 promoter-dependent transcriptional activities by sesamol.
abstract: Cyclooxygenase-2 (COX-2) has been shown to play an important role in colon carcinogenesis. Moreover, one of the components of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, NADPH oxidase 1 (NOX1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. We have reported that sesamol, one of the lignans in sesame seeds, suppressed COX-2 gene transcriptional activity in human colon cancer cells, and also suppressed intestinal polyp formation in Apc-mutant mice. In the present study, we investigated the involvement of NADPH oxidase in the inhibition of COX-2 transcriptional activity by sesamol. We found that several NADPH oxidase inhibitors, such as apocynin, showed suppressive effects on COX-2 transcriptional activity. Moreover, sesamol significantly suppressed NOX1 mRNA levels in a dose-dependent manner. In addition, we demonstrated that knockdown of NOX1 successfully suppressed COX-2 transcriptional activity. These results suggest that inhibition of NADPH oxidase, especially NOX1, may be involved in the mechanism of the suppression of COX-2 transcriptional activity by sesamol.
authors.affiliation: Division of Cancer Prevention Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan ; Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Oga-gun, Gunma 374-0193, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Division of Cancer Prevention Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Ishigamori
authors.affiliation: Division of Cancer Prevention Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Fujii
authors.affiliation: Central Animal Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Cancer Prevention Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan ; School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Wakana
authors.initials: W
authors.lastname: Onuma
authors.affiliation: Department of Health and Environmental Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Terasaki
authors.affiliation: Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Oga-gun, Gunma 374-0193, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yano
authors.affiliation: Division of Cancer Prevention Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
keywords: NADPH oxidase; colon cancer; cyclooxygenase-2; sesame; sesamol