Effects of curcuminoids on breast cancer cell secretion of the bone-resorptive peptide parathyroid hormone-related protein (PTHrP) and on lytic breast cancer bone metastasis were evaluated.
In vitro, transforming growth factor (TGF)-β-stimulated PTHrP secretion was inhibited by curcuminoids (IC50 = 24 μM) in MDA-MB-231 human breast cancer cells independent of effects on cell growth inhibition.
Effects on TGF-β signaling revealed decreases in phospho-Smad2/3 and Ets-1 protein levels with no effect on p-38 MAPK-mediated TGF-β signaling.
In vivo, mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle and treated ip every other day with curcuminoids (25 or 50 mg/kg) for 21 days.
Osteolytic bone lesion area was reduced up to 51% (p < 0.01).
Consistent with specific effects on bone osteolysis, osteoclast number at the bone–tumor interface was reduced up to 53% (p < 0.05), while tumor area within bone was unaltered.
In a separate study, tumor mass in orthotopic mammary xenografts was also unaltered by treatment.
These data suggest that curcuminoids prevent TGF-β induction of PTHrP and reduce osteolytic bone destruction by blockade of Smad signaling in breast cancer cells.
Effects on TGF-β signaling revealed decreases in phospho-Smad2/3 and Ets-1 protein levels with no effect on p-38 MAPK-mediated TGF-β signaling.
In vivo, mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle and treated ip every other day with curcuminoids (25 or 50 mg/kg) for 21 days.
Osteolytic bone lesion area was reduced up to 51% (p < 0.01).
Consistent with specific effects on bone osteolysis, osteoclast number at the bone–tumor interface was reduced up to 53% (p < 0.05), while tumor area within bone was unaltered.
In a separate study, tumor mass in orthotopic mammary xenografts was also unaltered by treatment.
These data suggest that curcuminoids prevent TGF-β induction of PTHrP and reduce osteolytic bone destruction by blockade of Smad signaling in breast cancer cells.
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