Bamboo shavings (Bambusae Caulis in Taeniam, BCT) are widely used as a traditional Chinese medicine to control hypertension and cardiovascular disease, and to alleviate fever, vomiting, and diarrhea. It has been demonstrated that BCT reduces ovalbumin-induced airway inflammation by regulating pro-inflammatory cytokines, and decreases tumor growth in tumor-bearing mice. However, the effects of BCT on the metastatic potential of malignant cancer cells and the detailed mechanism of its anti-metastatic activity have not been examined previously. In this study, we investigated whether an aqueous extract of BCT (AE-BCT) reduces the metastatic potential of HT1080 cells, and elucidated the underlying anti-metastatic mechanism. In addition, we examined whether AE-BCT administration inhibits pulmonary metastasis of intravenously injected B16F10 cells in C57BL/6J mice. AE-BCT (50–250 µg/ml) dose-dependently suppressed colony-forming activity under anchorage-dependent and -independent growth conditions. Pretreatment with AE-BCT efficiently inhibited cell migration, invasion, and adhesion. AE-BCT also dramatically suppressed PMA-induced MMP-9 activity and expression by blocking NF-κB activation and ERK phosphorylation. Production of intracellular ROS, a key regulator of NF-κB-induced MMP-9 activity, was almost completely blocked by pretreatment with AE-BCT. Furthermore, daily oral administration of AE-BCT at doses of 50 and 100 mg/kg efficiently inhibited lung metastasis of B16F10 cells injected into the tail veins of C57BL/6J mice with no systemic toxicity. These results demonstrate that AE-BCT significantly reduced the metastatic activity of highly malignant cancer cells by suppressing MMP-9 activity via inhibition of ROS-mediated NF-κB activation. These results indicate that AE-BCT may be a safe natural product for treatment of metastatic cancer.

Abstract. The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H 2 O 2 content, as determined using H 2 O 2 -sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H 2 O 2 and uPAR expression. In addition, exogenous H 2 O 2 was found to increase uPAR mRNA expression and its promoter activity. Sitedirected mutagenesis of the potential NF-κB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-κB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutatedtype NF-κB-inducing kinase and I-κB, and a specific inhibitor of NF-κB (BAY11-7082) decreased the H. pyloriinduced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-κB. With the aid of NAC and H 2 O 2 , it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-κB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-κB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells.

BackgroundSsanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.MethodCellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.ResultsSHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.ConclusionSHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.

KIOM-C, a novel herbal formula, was recently reported to be effective for treating pigs suffering from porcine circovirus-associated disease (PCVAD). In addition, administration of KIOM-C promoted clearance of influenza virus via production of antiviral cytokines, such as TNF-α and IFN-γ. Since metastasis is the major cause of cancer-related death and the greatest challenge in cancer treatment, we investigated the effect of KIOM-C on the metastatic potential of HT1080 and B16F10 cells. We observed inhibitory properties of KIOM-C in colony-forming activity, migration and invasion. Matrix metalloproteinase-9 (MMP-9) activity in the resting and PMA-stimulated state in HT1080 cells was dose-dependently decreased by KIOM-C treatment via suppression of NF-κB activation. In addition, daily oral administration of KIOM-C at doses of 170 and 510 mg/kg, the corresponding human adult daily doses, efficiently blocked lung metastasis in C57BL/6J mice following injection of B16F10 cells in the tail veins. In particular, none of the mice administered KIOM-C during the experimental period exhibited systemic toxicity, such as body weight loss or liver and kidney dysfunction. Collectively, our results suggest that KIOM-C is a potential therapeutic formula useful as a safe herbal medicine for controlling metastatic cancer.

BackgroundDental caries is considered to be a preventable disease, and various antimicrobial agents have been developed for the prevention of dental diseases; however, many bacteria show resistance to existing agents. In this study, 14 medicinal herbs were evaluated for antimicrobial activity against five common oral bacteria as a screen for potential candidates for the development of natural antibiotics.MethodsAqueous extracts of medicinal herbs were tested for activity against Enterococcus faecalis, Actinomyces viscosus, Streptococcus salivarius, Streptococcus mutans, and Streptococcus sanguis grown in brain heart infusion (BHI) broth. A broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). A disk diffusion assay was performed by inoculating bacterial cultures on BHI agar plates with paper disks soaked in each of the medicinal herb extracts. Inhibition of the synthesis of water-insoluble glucans by S. mutans was also investigated.ResultsThe aqueous extracts of many of the 14 medicinal herbs demonstrated antimicrobial activity against the five types of pathogenic oral bacteria. The extracts of Sappan Lignum, Coptidis Rhizoma, and Psoraleae Semen effectively inhibited the growth of oral bacteria and showed distinct bactericidal activity. The extracts of Notoginseng Radix, Perillae Herba, and Psoraleae Semen decreased the synthesis of water-insoluble glucans by the S. mutans enzyme glucosyltransferase (GTase). The present study is the first to confirm the antimicrobial activity of the extract of Sappan Lignum against all five species of oral bacteria strains.ConclusionThese results suggest that certain herbal medicines with proven antimicrobial effects, such as Sappan Lignum and Psoraleae Semen, may be useful for the treatment of dental diseases.