Obesity is frequently associated with
breast cancer. Such associations are possibly mediated by
adipokines.
Visfatin, an
adipokine, has recently been shown to be related to the development and progression of
breast cancer. Therefore, the down-regulation of
visfatin may be a novel strategy for
breast cancer therapy.
Curcumin has anticancer activities by modulating multiple signaling pathways and genes. The purpose of this study was to investigate whether
visfatin gene expression is affected by
curcumin in human
breast cancer cells and to characterize the functional role of
visfatin in
breast cancer. We found that the
mRNA and
protein levels of
visfatin were down-regulated by
curcumin in MDA-MB-231, MDA-MB-468, and MCF-7
breast cancer cells, along with decreased activity of constitutive nuclear factor (NF)-κB. We confirmed the repressive effect of
curcumin on
visfatin transcription by performing a
visfatin promoter-driven reporter assay and identified two putative NF-κB-binding sites on
visfatin promoter that are important for this effect. EMSA and
chromatin immunoprecipitation analysis indicated the binding of p65 to the
visfatin promoter, which was effectively blocked by
curcumin. Enforced expression of p65
protein increased
visfatin promoter activity, whereas blocking NF-κB signaling suppressed
visfatin gene expression.
Visfatin could enhance the invasion of MDA-MB-231 cells and also attenuate
curcumin-induced inhibition of cell invasion; on the other hand,
visfatin knockdown by
small interfering RNA led to the reduction of cell invasion. Our data demonstrate, for the first time, that
curcumin down-regulates
visfatin gene expression in human
breast cancer cells by a mechanism that is, at least in part, NF-κB dependent and suggest that
visfatin may contribute to
breast cancer cell invasion and link
obesity to
breast cancer development and progression.