Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

• Published in: Nutrients Vol. 9; no. 3; p. 300
• Main Authors: Liu, Mandy M, Huang, Kevin M, Yeung, Steven, Chang, Andy, Zhang, Suhui, Mei, Nan, Parsa, Cyrus, Orlando, Robert, Huang, Ying
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.03.2017; MDPI
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - toxicity; Activation; Ames test; Animals; Anthracene; Anticarcinogenic Agents - pharmacology; Antioxidants; AP-1; Biocompatibility; cancer prevention; Carcinogenesis; Carcinogens; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line, Tumor; Cell Transformation, Neoplastic - drug effects; Deoxyribonucleic acid; DMBA; DNA; DNA Damage - drug effects; Drugs, Chinese Herbal - pharmacology; EGF; Epidermal growth factor; Female; Gene Expression Regulation; Genes, Reporter; Herbal medicine; Herbs; Hyperplasia; Hyperplasia - etiology; Hyperplasia - prevention & control; In vitro methods and tests; In vivo methods and tests; JB6; Mice; Mice, Inbred SENCAR; Mutagenicity; Mutation; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; Promoters; Promotion; Rodents; SENCAR mice; Skin; Skin - drug effects; Skin - pathology; skin cancer; SWT; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transformations; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; NF-κB; SWT; skin cancer; Ames test; SENCAR mice; cancer prevention; EGF; DMBA; AP-1; JB6
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu9030300

Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women's diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT's activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF)-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in 'Sensitivity to Carcinogenesis' (SENCAR) mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA), and H- mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.