Submitted to: American Association of Cancer Research Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 12/5/2012
Publication Date: 1/20/2013
Citation: Yan, L. 2013. Curcumin deteriorates trabecular and cortical bone in mice bearing metastatic Lewis lung carcinoma. American Association of Cancer Research Meeting. [abstract] In: Proceedings of the AACR Special Conference on tumor Invasion and Metastasos; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA); AACR; Cancer Prev Res 2013;73(3 Suppl): Abstract no B77.
Technical Abstract: Bone is a major target of metastasis for many malignancies; curcumin has been studied for its role in cancer prevention including early phase clinical trials for its efficacy and safe use with cancer patients. The present study investigated the effects of dietary supplementation with curcumin (2% and 4%) on (1) pulmonary metastasis of Lewis lung carcinoma and (2) bone microstructural changes in female C57BL/6 mice. Curcumin significantly increased the size of lung metastases, which was accompanied with significant increases in plasma concentrations of angiogenic factors (e.g. angiogenin, VEGF) and inflammatory cytokines (e.g. IL-1ß, MCP-1). Morphometric analysis showed that curcumin at 2% and 4% dietary levels significantly reduced bone volume to total volume ratio (BV/TV), connective density (Conn.D.) and trabecular number (Tb.N.) and significantly increased structure model index (SMI, an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation (Tb.Sp.) in vertebral bodies, and at the 4% level curcumin significantly reduced BV/TV and Tb.N. and at either level it significantly reduced trabecular thickness (Tb.Th.) in distal femurs compared with the controls. In the mid-shaft of femur, curcumin at the 4% level significantly reduced cortical bone area to total area ratio (Ct.Ar/Tt.Ar.) and cortical thickness (Ct.Th.) compared with the controls. Furthermore, curcumin feeding resulted in dose-dependent decreases in plasma concentrations of osteocalcin (a marker of bone formation) and increases plasma tartrate-resistant acid phosphate 5b (a marker of bone resorption) compared with the controls, indicating that curcumin may deteriorate trabecular and cortical bone by disrupting the balance of bone remodeling. As skeleton is a favored site of metastasis for many cancers, our results that curcumin (1) enhances metastatic growth and (2) results in osteolytic deterioration of bone suggest the need of assessment of bone structural changes for curcumin cancer prevention studies, particularly for human trials with cancer patients who are the risk of malignant spread, to determine the curcumin effects and its interaction with malignancy on skeleton health.