The dietary plant derived anti-oxidant, Curcumin, has been proposed for cancer chemoprevention. 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), a inflammation

and cell survival related transcription factor. Here we addressed early effects of Curcumin in MDA-MB-231 breast cancer cells using microarray gene expression analyses. After 6 hours of treatment, Curcumin significantly down-regulates transcription of the inflammatory cytokines CXCL1 and -2 (GROα and -β) that translates into a reduction of the related proteins. This effect is

NFκB dependent since silencing of the NFκB subunit p65 leads to a reduction in CXCL1 and -2 mRNA levels. MDA-MB-231 cells do not express the CXCL1 and -2 receptor (interleukin 8 receptor B). CXCL1 and -2 repression is therefore expected to affect tumor growth, invasion and metastasis indirectly through reduced tumor inflammation and angiogenesis. Consistent with this, we observed that the number but not growth, vitality or

histology of lung metastases formed after intracardiac injection of MDA-MB-231 cells in immunodeficient mice was significantly reduced by Curcumin. These data show that Curcumin not only exerts anti-proliferative and pro-apoptotic activities but reduces metastatic dissemination most probably through down-regulation of NFκB dependent transcription. Curcumin therefore appears suitable as an adjuvant for breast cancer chemoprevention.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA