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

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.

The β-Blocker Carvedilol Prevented Ultraviolet-Mediated Damage of Murine Epidermal Cells and 3D Human Reconstructed Skin

“…It exhibits two distinct antioxidant properties [11]: first, it is a chemical antioxidant with an ability to bind to and scavenge reactive oxygen species (ROS); second, it has pharmacological activity that suppresses ROS production. Since oxidative stress plays an essential role in UV-induced skin carcinogenesis and antioxidants have been proposed as skin cancer preventive agents [13][14][15], we hypothesized that the antioxidant property of carvedilol is responsible for its skin cancer preventive effects. Supporting this hypothesis, carvedilol has been reported to have an inhibitory activity against hydroxyl radical production [3], lipid peroxidation [16], and apoptosis [17], but has not been evaluated in UV-associated skin models.…”

Review of the Efficacy and Mechanisms of Traditional Chinese Medicines as a Therapeutic Option for Ionizing Radiation Induced Damage

“…This Prescription promotes hematopoietic and immune system recovery after irradiation by increasing the number of peripheral white blood cells and bone marrow colony-forming units ( Liang et al, 2006 ). Studies revealed that Siwu Tang induces the antioxidant Nrf2 pathway, partially inhibits DNA damage, prevents the activation of nuclear transcription factor activating protein-1 (AP-1) and NF-κB, thereby, inhibiting ionizing radiation-induced damage and oncogenesis ( Liu et al, 2017 ).…”