Abstract
Bone metastasis is a severe complication of advanced breast cancer, resulting in osteolysis and increased mortality in patients. Raddeanin A (RA), isolated from traditional Chinese herbs, is an oleanane-type triterpenoid saponin with anticancer potential. In this study, we investigated the effects of RA in breast cancer-induced osteolysis and elucidated the possible mechanisms involved in this process. We first verified that RA could suppress osteoclast formation and bone resorption in vitro. Next, we confirmed that RA suppressed Ti-particle-induced osteolysis in a mouse calvarial model, possibly through inhibition of the SRC/AKT signaling pathway. A breast cancer-induced osteolysis mouse model further revealed the positive protective effects of RA by micro-computed tomography and histology. Finally, we demonstrated that RA inhibited invasion and AKT/mammalian target of rapamycin signaling and induced apoptosis in MDA-MB-231 cells. These results indicate that RA is an effective inhibitor of breast cancer-induced osteolysis.
Highlights
Introduction Anemone raddeanaRegel has been widely used to treat cancer, rheumatism, and neuralgia[1,2,3]
RANKL differentiated bone marrow-derived macrophages (BMMs) into mature tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts, but Raddeanin A (RA) produced an inhibitory effect on the formation of TRAPpositive multinucleated osteoclasts in a concentrationdependent manner (Fig. 1a, b)
These evidences suggested that RA prevented RANKL-induced osteoclast formation in vitro
Summary
Regel has been widely used to treat cancer, rheumatism, and neuralgia[1,2,3]. This traditional Chinese medicinal herb belongs to the Ranunculaceae family and exhibits antitumor efficacy, anti-inflammatory efficacy, and analgesic activity[4]. Recent studies have demonstrated that RA can prevent proliferation, induce apoptosis, and inhibit invasion in various human tumor cells, including gastric cancer cells, hepatocellular carcinoma cells, and nonsmall-cell lung carcinoma cells[6,7,8]. The mechanisms through which RA exerts these effects may be attributed to its ability to inhibit angiogenesis by preventing the phosphorylation of vascular endothelial growth factor receptor 2 and associated protein kinases, including phospholipase C γ1, Janus kinase 2, focal adhesion kinase, Src, and AKT9. RA may be a promising agent with broad antitumor effects
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