In the current study, we attempted to estimate whether liensinine and nuciferine could prevent breast cancer-mediated bone destruction by examining their effects on the growth, motility, and invasiveness of human triple-negative MDA-MB-231 and human estrogen receptor-positive MCF-7 cells, RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs), and mature osteoclast-mediated bone resorption. The gene discussed is TNFSF11; the disease is breast cancer.