Curcumin Reverses Breast Tumor Exosomes Mediated Immune Suppression of Nk Cell Tumor Cytotoxicity.
From: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Huang-Ge.Zhang@ccc.uab.edu
Biochimica et biophysica acta
- Publish Date: Jul 2007
- ISSN: 0006-3002
- Volume: 1773
- Issue: 7
- Pages: 1116-23
- Medium: Print
- Language: English
- Citation (JAMA): Zhang Huang-Ge, Kim Helen, Liu Cunren, et al. Curcumin Reverses Breast Tumor Exosomes Mediated Immune Suppression of Nk Cell Tumor Cytotoxicity.. Biochim. Biophys. Acta Jul 2007;1773:1116-23
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.
Mesh Headings (Keywords): Animals, Antineoplastic Agents, Breast Neoplasms, Cell Line, Tumor, Curcumin, Enzyme Activation, Female, Humans, Immune System, Interleukin-2, Janus Kinase 3, Killer Cells, Natural, Mice, Neoplasm Proteins, Ubiquitin
Check for Full Text / PubMed Unique Identifier (PMID): 17555831
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