Abstract 826: Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis

Abstract

Abstract Breast cancer is a major public health issue for women worldwide and 70% of the disease preferentially metastasizes to bone resulting in its destruction. Advanced breast cancer releases osteoclastogenic factors to promote bone resorption. As bone metastasis with breast cancer is associated with high mortality, osteoclastogenesis is a potential therapeutic target. We have shown previously that benzyl isothiocyanate (BITC), which is present in edible cruciferous vegetables, inhibits breast cancer development in a transgenic mouse model. The present study was designed to determine effect of BITC on breast cancer-induced osteoclastogenesis. We employed well-established in vitro osteoclast co-culture system of Raw 264.7 murine macrophage cells with human breast cancer cells for this assessment. BITC treatment significantly inhibited the number as well as size of osteoclasts in a dose dependent manner in every co-culture experiment. In addition, BITC downregulated both mRNA and protein levels of macrophage colony stimulating factor (MCSF) and receptor activator of NF-êB ligand (RANKL) which are key factors for formation of osteoclasts. Moreover, receptor activator of NF-êB ligand (RANKL)-induced osteoclast differentiation as well as bone resorption was suppressed in the presence of BITC. On the other hand, BITC induced osteoprotegerin (OPG) acting as a decoy receptor of RANKL and negatively regulated osteoclast formation. Quantitative PCR analysis revealed that mRNA levels of osteoclastogenesis-related cytokines and proteins (IL-1â, IL-6, TNF-á, GM-CSF, OPG, RUNX2) were repressed in BITC-treated breast cancer cells. Taken together, BITC showed inhibitory activity on breast cancer-mediated osteoclastogenesis. This study was supported by the grant CA129347 awarded by the National Cancer Institute. Citation Format: Subrata K. Pore, Anuradha Sehrawat, Shivendra V. Singh. Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 826.