Gold clusters prevent breast cancer bone metastasis by suppressing tumor-induced osteoclastogenesis.

: Bone is the most frequent site for breast cancer metastasis, which accounts for the leading cause of death in advanced breast cancer patients. Serious skeletal-related events (SREs) caused by bone metastasis have a decisive impact on the life expectancy of breast cancer patients, making breast cancer almost incurable. Metastatic breast cancer cell induced pathological osteoclastogenesis is a key driver of bone metastasis and osteolytic bone lesions. We previously reported that gold clusters can prevent inflammation induced osteoclastogenesis and osteolysis . In this study, we investigated the effects of a BSA-coated gold cluster on metastatic breast cancer-induced osteoclastogenesis and tumor-induced osteolysis , and elucidated its possible mechanism. : Breast cancer cell line MDA-MB-231 was used to evaluate the regulatory effects of gold clusters on breast cancer metastasis and tumor induced osteoclastogenesis . Cell counting kit-8, transwell, wound-healing and colony formation assays were performed to evaluate the effect of gold clusters on proliferation and metastasis of MDA-MB-231 cells. Tartrate-resistant acid phosphatase (TRAP) staining and filamentous-actin rings analysis were used to detect the regulatory effects of gold clusters on MDA-MB-231 cell-conditioned medium (MDA-MB-231 CM) triggered and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in mouse bone marrow-derived mononuclear cells (BMMs). A mouse model of breast cancer bone metastasis was used to evaluate the activity of the gold cluster on the tumor induced osteolysis. : The gold clusters suppressed the migration, invasion and colony formation of MDA-MB-231 cells in a dose-dependent manner . The gold clusters strongly inhibited both MDA-MB-231 CM triggered and RANKL-induced osteoclast formation from BMMs . Cell studies indicated that the gold clusters suppressed the expression of osteolysis-related factors in MDA-MB-231 cells and inhibited the subsequent activation of NF-κB pathway in BMMs. Treatment with the clusters at a dose of 10 mg Au/kg.bw significantly reduces the breast cancer cell induced osteolysis . : Therefore, the gold clusters may offer new therapeutic agents for preventing breast cancer bone metastasis and secondary osteolysis to improve patient outcomes.