title: Curcumin down-regulates visfatin expression and inhibits breast cancer cell invasion.
abstract: 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.
authors.affiliation: School of Dentistry, Yangsan Campus of Pusan National University, Yangsan, 626-870, South Korea. skbae@pusan.ac.kr.
authors.forename: Su-Ryun
authors.initials: SR
authors.lastname: Kim
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Bae
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Wee
authors.forename: Il
authors.initials: I
authors.lastname: Yun
authors.forename: Hye-Ock
authors.initials: HO
authors.lastname: Jang
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020218:Response Elements
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D016328:NF-kappa B; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D003474:Curcumin