ABSTRACT
BACKGROUND: Cudratricusxanthone A (CTXA) was isolated from Cudrania tricuspidata and its anti-inflammatory, hepatoprotective, and anti-proliferative activities have previously been studied in vitro. However, effects of CTXA on osteoclast differentiation have not been investigated. PURPOSE: In this study, the effect of CTXA from C. tricuspidata on in vitro osteoclastogenesis was studied. DESIGN/METHODS: CTXA was isolated from the roots of C. tricuspidata. The effects of CTXA on the RANKL-induced osteoclastogenesis, actin ring formation, and bone resorption were tested by using the RAW 264.7 cells and mouse bone marrow monocytes (BMMs). RESULTS: The structure of CTXA was identified by comparison with spectral data in the literature. We also checked the effect of CTXA on in vitro osteoclastogenesis. CTXA significantly inhibited the JNK/MAPK signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells and BMMs. Moreover, it inhibited RANKL-induced expression of c-Fos and NFATc1. CONCLUSION: In conclusion, CTXA suppresses osteoclast differentiation by inhibiting RANKL-induced MAPK signaling and attenuates bone resorption by disrupting actin ring formation in mature osteoclasts. These results suggest that CTXA inhibits bone resorption through an inhibitory effect on osteoclast formation and function.
Subject(s)
Osteoclasts/drug effects , Xanthones/chemistry , Xanthones/pharmacology , Animals , Bone Marrow Cells/drug effects , Bone Resorption/drug therapy , Cell Differentiation/drug effects , MAP Kinase Signaling System/drug effects , Male , Mice , Mice, Inbred ICR , Moraceae/chemistry , Osteoclasts/cytology , Osteoclasts/physiology , Plant Roots/chemistry , Proto-Oncogene Proteins c-fos/metabolism , RANK Ligand/metabolism , RANK Ligand/pharmacology , RAW 264.7 Cells , Signal Transduction/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Cudrania tricuspidata is a deciduous tree found in Korea, China, and Japan. C. tricuspidata contains an abundance of various minerals, B vitamins, and flavonoids to help prevent diverse cancers. Cudratricusxanthone A (CTXA), a compound isolated from the roots of C. tricuspidata, has potent anti-proliferative, antioxidative, and monoamine oxidase inhibitory effects. AIM OF THE STUDY: In the present study, cudratricusxanthone A (CTXA) is a xanthone isolated from the bioassay-guided fractionation of the EtOH extract of C. tricuspidata with strong anti-cancer activity in breast cancer cells. The effect of CTXA on cell migration and apoptosis were evaluated in the MCF-7 and MDA-MB-231 human breast carcinoma cell lines. MATERIALS AND METHODS: Effects of CTXA on phorbol 12-myristate 13-acetate (PMA)-induced MCF-7 and MDA-MB-231 cells. Flow cytometric measurements of CTXA-induced apoptosis in breast cancer cells. RESULTS: The results show that CTXA gradually reduced viability of the two breast cancer cell lines and induced apoptosis in a concentration-dependent manner. Moreover, CTXA effectively blocked breast cancer cell migration and invasion. CTXA decreased the expression of matrix metalloproteinase-9, extracellular regulated kinases 1 and 2 and phosphorylation of the inhibitor IκBα in the MCF-7 and MDA-MB-231 cell lines. CONCLUSIONS: Collectively, these results indicate that CTXA possesses anti-cancer activities and provide a basis for developing effective therapeutic agents to inhibit growth and metastasis of breast cancer.
