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.