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.
Fungal cell walls have essential roles in the life of the fungal cell. They protect mechanically the cell from the environment, prevent osmotic bursting of the cell by the tugor pressure and act as a sieve for large molecules that might harm the cell membrane. 1)Chitin, along with (1,3)-b-D-glucan, represents the main structural components of the fungal cell wall. As a crystalline polymer composed of b-1,4-linked homopolymer of N-acetylglucosamine (GlcNAc), chitin contributes to the rigidity of the cell wall.2) It is synthesized on the cytoplasmic surface of the plasma membrane, extruded perpendicularly to the cell surface as microfibrils and crystallized outside the cell through extensive hydrogen bonding as a-chitin (the polyGlcNAc chains run antiparallel).3) Chitin is synthesized by chitin synthase 1 (ScCHS1p), 2 (ScCHS2p), and 3 (ScCHS3p) in Saccharomyces cerevisiae. 4,5) Among them, chitin synthase 1 is a nonessential repair enzyme, 5) whereas chitin synthase 2 and 3 are essential enzymes in primary septum formation 6) and bud ring formation, 7) respectively. Although the content of chitin in the fungal cell wall varies from species to species, 8) its synthesis constitutes a model for fungal morphogenesis. Thus, specific inhibitors of chitin synthase 2 and 3 might serve as interesting lead compounds for the development of effective antifungal agents.The Chloranthus japonicus (Chloranthaceae) is a perennial herb that grows in the southern part of Korea, Japan, and China. This plant has been long recognized to be useful for boils, dermatopathy, and enteric fever in Korea as a folk remedy.9) Recently, shizukaol B, cycloshizukaol A, and shizukaol F isolated from the roots of Chloranthus japonicus were reported as cell adhesion inhibitors.10) In addition, many plants of the genus Chloranthus have been used in Chinese folk medicine for the treatment of bone fractures.11) A number of sesquiterpenoids 12,13) and sesquiterpenoid oligomers 14,15) have been isolated from the genus Chloranthus, and a quite recent study showed that chlorahololides A and B isolated from Chloranthus holostegius were potent and selective blockers of potassium channel. 16)In the course of search for chitin synthase 2 inhibitors from plant extracts, a novel type of chitin synthase 2 inhibitor was found in the methanol extract of the whole bodies of C. japonicus Sieb. Although the extract of C. japonicus has been long recognized to be useful as a folk remedy in Korea,9) this is the first report that the extract of C. japonicus could be used as antifungal agents by the inhibition of chitin synthase 2. Here, we describe the isolation and structure elucidation of a novel sesquiterpene furan compound CJ-01, and its inhibitory activities against chitin synthase 2 of S. cerevisiae and various human and phytopathogenic fungi. A novel sesquiterpene furan compound CJ-01 was isolated from the methanol extract of the whole plant of Chloranthus japonicus SIEB. by monitoring the inhibitory activity of chitin synthase 2 from Saccharomyces cerevisiae. Based...
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