Bone is one of the metastatic sites for advanced breast cancer. Nearly 70% of breast cancer patients experience metastasis to bone due to enhanced osteoclastogenesis and formation of osteoclasts leading to bone resorption. We have shown previously that benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables such as garden cress, is a potent inhibitor of breast cancer cells in vitro and in vivo. The present study was designed to determine the effect of BITC on breast cancer-induced osteoclastogenesis. Co-culture of murine RAW 264.7 macrophages with human breast cancer cells resulted in genesis of osteoclasts in vitro that was suppressed significantly in the presence of BITC. Runx2, a transcription factor, is abnormally expressed in breast cancer and contributes to osteoclastogenesis by regulating receptor activator of NF-κB ligand (RANKL). BITC treatment downregulated expression of Runx2 in breast cancer cells at the mRNA and protein levels. Osteoclastogenesis was increased in Runx2 overexpressing MDA-MB-231 cells, whereas conditional knockdown of Runx2 in T47D cells attenuated this process. To determine the in vivo efficacy of BITC, MDA-MB-231-Luc cells were injected into the left ventricle of nude mice. BITC was administrated orally at 10 mg per kg body weight. Micro-CT X-ray analysis showed that bone metastases and erosion was decreased by about 50% upon BITC treatment when compared with vehicle control. Cathepsin K and total RANKL levels were lower in the plasma of BITC-treated mice when compared to the control group. Altogether, this study demonstrates, for the first time, that BITC is a potent inhibitor of breast cancer-induced osteoclastogenesis in vivo. This study was supported by the grant RO1 CA129347-09 awarded by the national Cancer Institute.

Citation Format: Subrata K. Pore, Shivendra V. Singh. Benzyl isothiocyanate prevents breast cancer-induced bone erosion in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5258. doi:10.1158/1538-7445.AM2017-5258

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.