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Nutrients 2017, 9(3), 300; doi:10.3390/nu9030300

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

1
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA
2
Department of Pharmacology and Toxicology, Shanghai Institute for Food and Drug Control, Shanghai 201203, China
3
Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
4
Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA
*
Author to whom correspondence should be addressed.
Received: 9 February 2017 / Revised: 12 March 2017 / Accepted: 12 March 2017 / Published: 18 March 2017
(This article belongs to the Special Issue Antioxidants in Health and Disease)
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Abstract

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-ras 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. View Full-Text
Keywords: cancer prevention; DMBA; skin cancer; AP-1; NF-κB; SWT; SENCAR mice; EGF; JB6; Ames test cancer prevention; DMBA; skin cancer; AP-1; NF-κB; SWT; SENCAR mice; EGF; JB6; Ames test
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Liu, M.M.; Huang, K.M.; Yeung, S.; Chang, A.; Zhang, S.; Mei, N.; Parsa, C.; Orlando, R.; Huang, Y. Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang. Nutrients 2017, 9, 300.

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