title: The preventive role of breadfruit against inflammation-associated epithelial carcinogenesis in mice.
abstract: Artocarpus communis has been identified as a rich source of flavonoids and has been gaining attention for its potential chemopreventive abilities. In this study, methanol extracts from the fruit of A. communis (MEFA) and leaf of A. communis (MELA) were prepared, and their effects on inflammation-associated skin tumorigenesis were assessed using mouse models, including 12-O-tetradecanoylphorbol-13-acetate (TPA) induced cutaneous inflammation as well as 7,12-dimethylbenz[α]anthracene (DMBA) initiated and TPA-promoted skin tumorigenesis. According to the results, both MEFA and MELA decreased the intensity of leukocyte infiltration in mouse dorsal skin and cutaneous edema induced by TPA, which appeared to be mediated by inhibition of proinflammatory genes (inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), IL-1β, and IL-6) and proinflammatory mediators (TNF-α, IL-1β, and Prostaglandin E2 ). In addition, topical application with MEFA or MELA effectively attenuated tumor incidence, multiplicity, volume, malignancy as well as angiogenesis of TPA-stimulated skin tumor promotion in DMBA-initiated mice. Notably, immunohistochemical stain showed that MEFA and MELA attenuated COX-2 expression of both skin and tumor tissues in different animal tests, which may be closely related to the suppression of nuclear factor kappa B/activator protein signaling networks. These findings first demonstrate that flavonoid-rich A. communis may exert potent anti-inflammatory activity through modulation of COX-2 in TPA-activated skin and tumor tissues.
authors: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors: Jer-An
authors: JA
authors: Lin
authors: Hsiang-Chi
authors: HC
authors: Chen
authors: Gow-Chin
authors: GC
authors: Yen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D031622:Artocarpus / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D016588:Anticarcinogenic Agents; D010936:Plant Extracts; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate
keywords: 12-O-tetradecanoylphorbol-13-acetate; Artocarpus communis; Flavonoids; Inflammation; Skin tumorigenesis