Pitavastatin inactivates NF-κB and decreases IL-6 production through Rho kinase pathway in MCF-7 cells

The aim of the present study was to provide new mechanistic insight into the effect of pitavastatin at low dose on NF-kappa B activated by TNF-alpha in the human breast cancer cell line (MCF-7). We found that treatment of MCF-7 with 1 mu M pitavastatin inhibited the proliferation and suppressed the nuclear expression of NF-kappa B p65 induced by TNF-alpha with Western blotting. Furthermore, EMSA showed that pitavastatin significantly reduced the DNA binding activity of NF-kappa B induced by TNF-alpha.. Subsequently, luciferase assay revealed that pitavastatin (1 mu M) inhibited the transcriptional activity of the NF-kappa B promoter, which was clearly related to the HMG-CoA reductase activity because addition of mevalonic acid (MEV) could elevate the NF-kappa B activity. Moreover, the Rho kinase inhibitor Y27632 abolished the effect of pitavastatin on NF-kappa B activity. Finally, the addition of TNF-alpha significantly increased IL-6 protein production, which was suppressed by the addition of pitavastatin. These results suggest that pitavastatin at low dose (1 mu M) inhibits NF-kappa B activation and decreases IL-6 production induced by TNF-alpha. It is dependent on Rho kinase pathway in human breast cancer cells.