Liu Mandy M, Huang Kevin M, Yeung Steven, Chang Andy, Zhang Suhui, Mei Nan, Parsa Cyrus, Orlando Robert, Huang Ying
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Department of Pharmacology and Toxicology, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
Nutrients. 2017 Mar 18;9(3):300. 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.
探索传统药物可能会促成低成本且无毒的癌症预防药物的研发。四物汤（SWT）由熟地黄、当归、川芎和芍药四味草药组成，是治疗妇科疾病最常用的中药之一。在我们之前的研究中，体外和体内实验均表明四物汤能强烈诱导抗氧化剂Nrf2信号通路。由于Nrf2的激活与抗癌作用相关，本研究旨在评估四物汤的癌症预防活性。在艾姆斯试验中，四物汤对化学致癌物7,12-二甲基苯并(a)蒽（DMBA）诱导的致突变性表现出抗诱变活性。在JB6 P+细胞（一种用于研究肿瘤促进作用的非癌性小鼠表皮模型）中，四物汤抑制了表皮生长因子（EGF）诱导的肿瘤转化。荧光素酶报告基因检测表明，四物汤抑制了EGF诱导的AP-1激活以及TNF-α诱导的NF-κB激活，而这两种激活是皮肤致癌过程中的关键因素。在“对致癌作用的敏感性”（SENCAR）小鼠的DMBA诱导的皮肤增生试验中，局部和口服四物汤均抑制了DMBA诱导的表皮增生、增殖标志物增殖细胞核抗原（PCNA）的表达以及H-突变。这些发现首次证明，四物汤在体外和体内均可预防肿瘤促进剂和化学物质诱导的致癌作用，部分原因是通过抑制DNA损伤以及阻断AP-1和NF-κB的激活。
