ABSTRACT
Previous reports have documented that cholesterol-lowering simvastatin prevented osteolytic metastasis of breast cancer in animal model in which cancer cells were placed into blood circulation. Thus, simvastatin treatment might have a preventive effect in inhibiting osteoclast activity of metastatic bone microenvironment. This study documented that both simvastatin and MBCD (cholesterol depleting drug) blocked the breast cancer-induced TRAP and MMP activity, and expressions of various osteoclastogenic genes (TRAP, Cathepsin K, and NFATc1) in pre-osteoclast RAW264.7 cells, and osteoclastogenic CSF-1 and RANKL expressions in breast cancer MCF-7 cells. Thus, these findings unravel a molecular mechanism of simvastatin-/MBCD-mediated inhibition of breast cancer-driven osteoclast activity.
Acknowledgment
Authors thank Prof. Alo Nag, Department of Biochemistry, University of Delhi South Campus, India, for providing some crucial reagents such as antibody (MMP-2).
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
Funding
Dr. Chandi C. Mandal was supported by UGC [30-49/2014 (BSR)], DBT [6242-P9/RGCB/PMD/DBT/CCML/2015], and Central University of Rajasthan, India. Tanu Sharma was supported by DST-INSPIRE fellowship [IF140765] provided by the Department of Science and Technology, India.