Format

Send to

Choose Destination
Pharmacol Res. 2019 Feb 20;142:140-150. doi: 10.1016/j.phrs.2019.02.015. [Epub ahead of print]

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

Author information

1
Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
2
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
3
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Electronic address: lliu@must.edu.mo.
4
Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: lixiaoj@smu.edu.cn.

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 preosteoclastic RAW264.7 cells while simultaneously downregulating CXCR1, the ligand of IL-8 related to bone destruction, during MDA-MB-231 CM-induced osteoclastogenesis. Previously, IL-8/CXCR1 was reported to be associated with the pathogenesis and progression of RA, and SIN was observed to markedly ameliorate bone erosion of RA patients. Our current findings may extend the utilization of SIN to preventing osteoclastogenesis and bone destruction in breast cancer patients and may enable IL-8/CXCR1 to serve as new targets for both anticancer and antiarthritic drug discovery.

KEYWORDS:

Breast cancer; CXCR1; IL-8; IL-8 (CID: 44357137); Lipopolysaccharides (PubCID: 1347); NFATc1; Osteoclast; Sinomenine; Sinomenine (CID:5459308); Zoledronic acid (CID:68740)

PMID:
30797069
DOI:
10.1016/j.phrs.2019.02.015

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center