Simvastatin and MBCD Inhibit Breast Cancer-Induced Osteoclast Activity by Targeting Osteoclastogenic Factors

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.

KEYWORDS:

• Breast cancer
• Bone metastasis
• Osteoclast activity
• Simvastatin
• Methyl beta cyclodextrin
• CSF-1
• RANKL

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.