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PMID: 17555831 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Biochimica et biophysica acta ·Vol. 1773 ·No. 7 ·2007-07-00 ·Pages 1116-23

Zhang HG, Kim H, Liu C, Yu S, Wang J, Grizzle WE, Kimberly RP, Barnes S

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 Terms
Animals Antineoplastic Agents/metabolism Breast Neoplasms/immunology,pathology Cell Line, Tumor Curcumin/metabolism Enzyme Activation Female Humans Immune System/physiology Interleukin-2/immunology Janus Kinase 3/metabolism Killer Cells, Natural/immunology Mice Neoplasm Proteins/metabolism Ubiquitin/metabolism
Chemicals
Antineoplastic Agents Interleukin-2 Neoplasm Proteins Ubiquitin Janus Kinase 3 Curcumin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhang Huang-Ge
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Huang-Ge.Zhang@ccc.uab.edu
Kim Helen
Liu Cunren
Yu Shaohua
Wang Jianhua
Grizzle William E
Kimberly Robert P
Barnes Stephen
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Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbamcr.2007.04.015
Email
huang-ge.zhang@ccc.uab.edu
Published
2007-07-00
Epub
2007-00-01
Pages
1116-23
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC2577190
Subset
IM
Grants
NCCIH NIH HHS · P50 AT-00477-07 · United States
NCI NIH HHS · U54 CA100949-04 · United States
NCCIH NIH HHS · P50 AT000477 · United States
NCI NIH HHS · R01 CA107181 · United States
NCI NIH HHS · U54 CA100949 · United States
NCI NIH HHS · R01 CA116092 · United States
NCI NIH HHS · R01 CA107181-03 · United States
NCI NIH HHS · R01 CA116092-03 · United States
External Links
PubMed source DOI: 10.1016/j.bbamcr.2007.04.015 PMC Full Text
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