Ma, N.N.MaLai, C.-S.C.-S.LaiChung, C.-H.C.-H.ChungYang, J.-M.J.-M.YangHsu, K.-C.K.-C.HsuChen, C.-Y.C.-Y.ChenChung, T.-S.T.-S.ChungLi, S.S.LiHo, C.-T.C.-T.HoMIN-HSIUNG PAN2018-09-102018-09-102014http://www.scopus.com/inward/record.url?eid=2-s2.0-84926421206&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/3851465-Demethyltangeretin (5-DTAN), an autohydrolysis product of tangeretin (TAN) found in citrus peel, exhibited more potent anti-proliferative activity in human cancer cells than TAN itself. In this study, we investigated the anti-tumor promoting effect and underlying molecular mechanism of 5-DTAN on 7,12-dimethyl-benz(a)anthracene (DMBA)-induced and 12-. O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin carcinogenesis. Application of 5-DTAN prior to each TPA-treatment was more effective than that of TAN on reducing the number, incidence and size of papillomas in DMBA-initiated mouse skin. Moreover, 5-DTAN suppressed cyclooxygenase-2 (COX-2) protein expression more strongly than TAN through interfering with phosphatidylinositiol 3-kinase (PI3K)/Akt signaling and further activation of transcription factor NF-κB. Taken together, these results revealed for the first time the in vivo chemopreventive efficacy of 5-DTAN on inhibition of skin carcinogenesis through promoting apoptosis and molecular interactions with residues of PI3K, COX-2, and AKT that may potentially serve as a novel functional agent capable of preventing inflammation-associated tumorigenesis. ? 2014 Elsevier Ltd.5-Demethyltangeretin; DMBA; Inflammation; Tangeretin; TPA[SDGs]SDG3Citrusjournal article10.1016/j.jff.2014.08.009