https://scholars.lib.ntu.edu.tw/handle/123456789/377952
Title: | Hexahydro-β-acids potently inhibit 12- O -tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice | Authors: | Hsu, C.-H. Ho, Y.-S. Lai, C.-S. SHU-CHEN HSIEH Chen, L.-H. Lin, E. Ho, C.-T. MIN-HSIUNG PAN |
Keywords: | cyclooxygenase-2 (COX-2); hexahydro-β-acids (HBA); inducible NO synthase (iNOS); inflammation; two-stage carcinogenesis | Issue Date: | 2013 | Journal Volume: | 61 | Journal Issue: | 47 | Start page/Pages: | 11541-11549 | Source: | Journal of Agricultural and Food Chemistry | Abstract: | We previously reported that hexahydro-beta-acids (HBAs), reduced derivatives of beta-acids (BA) from hop (Humulus lupulus L.), displayed more potent anti-inflammatory activity than BA in lipopolysaccharide-stimulated murine macrophages. In this study, we investigated the effects and underlying molecular mechanisms of hexahydro-β-acids (HBAs) on 12-O- tetradecanoylphorbol-13-acetate (TPA)-stimulated mouse skin inflammation and in the two-stage carcinogenesis model. Female ICR mice pretreated with HBA at 1 and 10 μg significantly reduced ear edema, epidermal hyperplasia, and infiltration of inflammatory cells caused by TPA. Molecular analysis exhibited that HBA suppressed iNOS, COX-2, and ornithine decarboxylase (ODC) protein and gene expression through interfering with mitogen-activated protein kinases (MAPKs) and phosphatidylinositiol 3-kinase (PI3K)/Akt signaling as well as the activation of transcription factor NF-κB. Furthermore, application of HBA (1 and 10 μg) prior to each TPA treatment (17.2 ± 0.9 tumors/mouse) resulted in the significant reduction of tumor multiplicity (5.1 ± 1.2, P < 0.01 and 2.3 ± 1.2, P < 0.001, respectively) in 7,12-dimethyl-benzanthracene (DMBA)-initiated mouse skin. The tumor incidence was significantly lowered to 75% (P < 0.05) and 58.7% (P < 0.01) by HBA pretreatment, respectively, and significantly reduced the tumor weight (0.34 ± 0.14 g, P < 0.01 and 0.09 ± 0.10 g, P < 0.001, respectively) as compared to DMBA/TPA-induced tumors (0.76 ± 0.04 g). ? 2013 American Chemical Society. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84889844306&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/377952 |
DOI: | 10.1021/jf403560r | SDG/Keyword: | Anti-inflammatory activity; Cyclooxygenase 2; inflammation; Mitogen activated protein kinase; Ornithine decarboxylase; Synthases; Tetradecanoylphorbol 13 acetates; two-stage carcinogenesis; Activation analysis; Amino acids; Gene expression; Mammals; Pathology; Volatile fatty acids; Tumors; antineoplastic agent; carboxylic acid; cyclooxygenase 2; immunoglobulin enhancer binding protein; inducible nitric oxide synthase; mitogen activated protein kinase; nonsteroid antiinflammatory agent; Nos2 protein, mouse; ornithine decarboxylase; phorbol 13 acetate 12 myristate; protein kinase B; Ptgs2 protein, mouse; animal; article; chemically induced disorder; chemistry; dermatitis; edema; female; Humulus; Institute for Cancer Research mouse; metabolism; mouse; skin tumor; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Carboxylic Acids; Cyclooxygenase 2; Dermatitis; Edema; Extracellular Signal-Regulated MAP Kinases; Female; Humulus; Mice; Mice, Inbred ICR; NF-kappa B; Nitric Oxide Synthase Type II; Ornithine Decarboxylase; Proto-Oncogene Proteins c-akt; Skin Neoplasms; Tetradecanoylphorbol Acetate |
Appears in Collections: | 食品科技研究所 |
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