Bisdemethoxycurcumin suppresses human osteosarcoma U-2 OS cell migration and invasion via affecting the PI3K/Akt/NF-kappa B, PI3K/Akt/GSK3 beta and MAPK signaling pathways in vitro

The metastasis of human osteosarcoma (OS) shows a difficult-to-treat clinical scenario and results in decreased quality of life and diminished survival rates. Finding or developing novel treatments to improve the life quality of patients is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was obtained from the rhizome of turmeric (Curcuma longa) and exerts antitumor activities in numerous human cancer cell lines. At present, there is no study showing BDMC effects on OS cell migration and invasion. In the present study, the effects of BDMC on cell migration and invasion of OS U-2 OS cells were investigated in vitro. Cell viability and proliferation were measured by flow cytometric and MTT assays, respectively. Cell motility, MMP-2 and -9 activity, and cell migration and invasion were assayed by scratch wound healing, gelatin zymography, and Transwell chamber assays, respectively. The protein expression levels were measured by western blotting. BDMC at 20 and 40 mu M significantly reduced total cell viability, and BDMC at 5 and 10 mu M significantly inhibited cell motility in U-2 OS cells. BDMC significantly suppressed the activities of MMP-2 and MMP-9 in U-2 OS cells. BDMC suppressed cell invasion and migration after 24 h treatment in U-2 OS cells, and these effects were in a dose-dependently manner. Results from western blotting indicated that BDMC significantly decreased the protein expression levels of PI3K/Akt/NF-kappa B, PI3K/Akt/GSK3 beta, and MAPK pathway in U-2 OS cells. Furthermore, BDMC inhibited uPA, MMP-2, MMP-9, MMP-13, N-cadherin, VE-cadherin, and vimentin but increased E-cadherin in U-2 OS cells. Based on these observations, it was suggested that BDMC may be a potential candidate against migration and invasion of human OS cells in the future.