Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFκB

Beatrice E. Bachmeier, Isabelle V. Mohrenz, Valentina Mirisola, Erwin Schleicher, Francesco Romeo, Clara Höhneke, Marianne Jochum, Andreas G. Nerlich, Ulrich Pfeffer

Research output: Contribution to journalArticlepeer-review

Abstract

The dietary antioxidant Curcumin has been proposed for cancer chemoprevention since it induces apoptosis and inhibits the formation of breast cancer metastases. Curcumin acts through the inhibition of phosphorylation of the inhibitor of kappa B (IκB), which in turn reduces the nuclear translocation of nuclear factor kappa B (NFκB), an inflammation- and cell survival-related transcription factor. However, it is not clear whether the strong antimetastatic effect can exclusively be explained by inhibition of NFκB. Here, we addressed the effects of Curcumin (IC50 = 17 μM) in MDA-MB-231 breast cancer cells using microarray gene expression analyses. Among the 62 genes whose expression was significantly altered, we found the two inflammatory cytokines CXCL1 and -2 (Groα and -β) that were downregulated. Further validation of the microarray results by quantitative real-time reverse transcription-polymerase chain reaction, western blots and enzyme-linked immunosorbent assay revealed that Curcumin impairs transcription of CXCL1 and -2 >24 h and reduces the corresponding proteins. Using small interfering RNA techniques, we elucidated the underlying molecular mechanism revealing that reduction of CXCL1 and -2 messenger RNA levels is NFκB dependent and requires intact IκBα expression. Moreover, CXCL1 and -2 silencing leads to downregulation of several metastasis-promoting genes among which we found the cytokine receptor CXCR4. We therefore suggest that the decrease of CXCL1 and -2 mediated by Curcumin is involved in the inhibition of metastasis.

Original languageEnglish
Pages (from-to)779-789
Number of pages11
JournalCarcinogenesis
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 2008

ASJC Scopus subject areas

  • Cancer Research

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