Sinomenine inhibits osteolysis in breast cancer by reducing IL-8/CXCR1 and c-Fos/NFATc1 signaling

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Yueyang ZhangXiaojuan Li

Abstract

Sinomenine (SIN) is an anti-inflammatory and antiarthritic alkaloid derived from Sinomenium acutum, and the product Zhengqing Fengtongning produced from SIN has been marketed in China for treating rheumatoid arthritis (RA). Interestingly, we recently found that SIN could significantly ameliorate bone destruction induced by breast cancer cells in mice. Micro-CT examination showed that bone loss of the trabecular bones in tumor-bearing mice was markedly decreased by i.p. treatment of SIN at 150 mg/kg body weight. A mechanistic study demonstrated that SIN could suppress osteoclast formation and bone absorption induced by both MDA-MB-231 cells and MDA-MB-231 cell-conditioned medium (MDA-MB-231 CM) in preosteoclastic RAW264.7 cells. The MDA-MB-231 CM-induced osteoclast-related genes TRAP and OSCAR were obviously downregulated by SIN. In addition, mRNA expression of c-Fos and NFATc1 and nuclear translocation of c-Fos and NFATc1 protein were inhibited by SIN during MDA-MB-231 CM-induced osteoclastogenesis, while NF-κB signaling was not impacted by SIN. More interestingly, SIN was demonstrated to decrease hIL-8 mRNA expression in cultured MDA-MB-231 cells and to inhibit hIL-8 protein expression in MDA-MB-231 cells cocultured with preos...Continue Reading

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