Pogostone attenuates osteolysis in breast cancer by inhibiting the NF-kB and JNK signaling pathways of osteoclast

Abstract

AimsBreast cancer is the most prevalent cancer in females, and approximately 70 % of all patients have evidence of metastatic bone disease, which substantially affects the quality of life and survival rate of breast cancer patients. Osteoporosis has become a global public health problem, and the abnormal activation of osteoclasts is the key to the progression of osteoporosis and the key to both diseases lies in the osteoclasts. Effective drug treatments are lacking and there is an urgent need to explore new drugs. Materials and methodsWe observed the effects of pogostone (PO) on osteoclast differentiation, bone resorption function and other indicators, and F-actin ring formation by using Trap staining, SEM and immunofluorescence, and further explored the targets of pogostone in regulating osteoclast differentiation and function using qPCR and Western Blot. In addition, we used CCK 8, Transwell, and flow cytometry to study the effects of pogostone on proliferation, invasion, migration, and apoptosis of MDA-MB-231 cells. Animal models were also constructed for in vivo validation. Key findingsPogostone inhibits osteoclast differentiation, bone resorption, formation of F-actin ring, and the expression of specific genes by attenuated NF-kB degradation and phosphorylation of JNK. In vitro, pogostone suppresses invasion of breast cancer cells, migration, and promotes their apoptosis. In mouse models, pogostone attenuated osteoclast formation and bone resorption, blocked breast cancer cells migration, and supprsed breast cancer-induced osteolysis and ovariectomized (OVX)-mediated osteoporosis. SignificanceThese biological functions of pogostone make it a potential drug for treatment of breast cancer-associated bone metastasis in the future.