Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang.
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-rasmutations. 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.
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. mmliu@westernu.edu.
Mandy M
MM
Liu
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. huang.2834@buckeyemail.osu.edu.
Kevin M
KM
Huang
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. skyeung@westernu.edu.
Steven
S
Yeung
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. chang.andy.y@gmail.com.
Andy
A
Chang
Department of Pharmacology and Toxicology, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. suhuizhangbc@gmail.com.|Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. suhuizhangbc@gmail.com.
Suhui
S
Zhang
Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. nan.mei@fda.hhs.gov.
Nan
N
Mei
Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA. cparsa@westernu.edu.
Cyrus
C
Parsa
Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA. rorlando@beverly.org.
Robert
R
Orlando
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. yhuang@westernu.edu.
Ying
Y
Huang
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D018632:Mice, Inbred SENCAR; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D002352:Carrier Proteins; D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; C561966:PAF protein, mouse; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C403258:si-wu-tang; D015127:9,10-Dimethyl-1,2-benzanthracene
AP-1; Ames test; DMBA; EGF; JB6; NF-κB; SENCAR mice; SWT; cancer prevention; skin cancer