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Abstract Title:

Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity.

Abstract Source:

Biochim Biophys Acta. 2007 Jul;1773(7):1116-23. Epub 2007 May 1. PMID: 17555831

Abstract Author(s):

Huang-Ge Zhang, Helen Kim, Cunren Liu, Shaohua Yu, Jianhua Wang, William E Grizzle, Robert P Kimberly, Stephen Barnes

Article Affiliation:

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Huang-Ge.Zhang@ccc.uab.edu

Abstract:

An important characteristic of tumors is that they at some point in their development overcome the surveillance of the immune system. Tumors secrete exosomes, multivesicular bodies containing a distinct set of proteins that can fuse with cells of the circulating immune system. Purified exosomes from TS/A breast cancer cells, but not non-exosomal fractions, inhibit (at concentrations of nanograms per ml protein) IL-2-induced natural killer (NK) cell cytotoxicity. The dietary polyphenol, curcumin (diferuloylmethane), partially reverses tumor exosome-mediated inhibition of natural killer cell activation, which is mediated through the impairment of the ubiquitin-proteasome system. Exposure of mouse breast tumor cells to curcumin causes a dose-dependent increase in ubiquitinated exosomal proteins compared to those in untreated TS/A breast tumor cells. Furthermore, exosomes isolated from tumor cells pretreated with curcumin have a much attenuated inhibition of IL-2 stimulated NK cell activation. Jak3-mediated activation of Stat5 is required for tumor cytotoxicity of IL-2 stimulated NK cells. TS/A tumor exosomes strongly inhibit activation of Stat5, whereas the tumor exosomes isolated from curcumin-pretreated tumor cells have a lowered potency for inhibition of IL-2 stimulated NK cell cytotoxicity. These data suggest that partial reversal of tumor exosome-mediated inhibition of NK cell tumor cytotoxicity may account for the anti-cancer properties of curcumin.

Study Type : In Vitro Study
Additional Links
Additional Keywords : Exosomes : CK(35) : AC(10)

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Sayer Ji
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