Rhodiola crenulata induces apoptosis in bone metastatic breast cancer cells via activation of caspase-9 and downregulation of MtMP activity

Breast cancer cells have the propensity to metastasize to bone, resulting in altered growth, chemoresistance, and causing skeletal failures, often leading to death in patients. There is a scarcity of effective therapeutics for bone metastasized breast cancer due to the lack of accurate drug screening metastasis models. We utilize a unique 3D in vitro nano clay-based scaffold model as a testbed for bone metastatic breast cancer for drug screening applications. Rhodiola crenulata, a Tibetan plant-based extract, has been previously explored for primary-site breast cancer. However, its effect on bone metastasized breast cancer cells is unknown. In the present study, we evaluated the cytotoxicity of R. crenulata extract on bone metastatic breast cancer using testbeds and compared the results with 2D cultured cells. We observed that R. crenulata induced apoptosis in bone metastasized breast cancer cells grown on a 3D in vitro testbed by upregulating pro-apoptotic proteins, p53, and caspase-9. Alternatively, we observed that bone cells remain unaffected by the treatment of R. crenulata. For the first time, we demonstrated the anticancer capabilities of R. crenulata against bone metastasis of breast cancer. R. crenulata is a robust therapeutic candidate for bone metastasis, shown to induce death in bone metastatic breast cancer while unaffecting healthy bone.