Premium
Inhibition of PKC‐Induced COX‐2 and IL‐8 Expression in Human Breast Cancer Cells by Glucosamine
Author(s) -
Chou WanYu,
Chuang KunHan,
Sun David,
Lee YuHsiu,
Kao PuHong,
Lin YenYu,
Wang HseiWei,
Wu YuhLin
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24955
Subject(s) - protein kinase c , cancer research , glucosamine , chemistry , cell growth , cancer cell , signal transduction , phosphorylation , inflammation , mapk/erk pathway , cancer , biology , medicine , biochemistry
Breast cancer is a common cancer leading to many deaths among females. Cyclooxygenase‐2 (COX‐2) and interleukin‐8 (IL‐8) are two highly expressed inflammatory mediators to be induced by the protein kinase C (PKC) signaling via various inflammatory stimuli and both contribute significantly to cancer metastasis/progression. Glucosamine has been shown to act as an anti‐inflammation molecule. The aim of this study was to clarify the role and acting mechanism of glucosamine during the PKC‐regulation of COX‐2/IL‐8 expression and the associated impact on breast cancer. In MCF‐7 breast cancer cells, glucosamine effectively suppresses the PKC induction of COX‐2 and IL‐8 promoter activity, mRNA and protein levels, as well as the production of prostaglandin E 2 (PGE 2 ) and IL‐8. Glucosamine is able to promote COX‐2 protein degradation in a calpain‐dependent manner and IL‐8 protein degradation in calpain‐dependent and proteasome‐dependent manners. The MAPK and NF‐κB pathways are involved in PKC‐induced COX‐2 expression, but only the NF‐κB pathway is involved in PKC‐induced IL‐8 expression. Glucosamine attenuates PKC‐mediated IκBα phosphorylation, nuclear NF‐κB translocation, and NF‐κB reporter activation. Both PGE 2 and IL‐8 promote cell proliferation and IL‐8 induces cell migration; thus, glucosamine appears to suppress PKC‐induced cell proliferation and migration. Furthermore, glucosamine significantly inhibits the growth of breast cancer xenografts and this is accompanied by a reduction in COX‐2 and IL‐8 expression. In conclusion, glucosamine seems to attenuate the inflammatory response in vitro and in vivo and this occurs, at least in part by targeting to the NF‐κB signaling pathway, resulting in an inhibition of breast cancer cell growth. J. Cell. Physiol. 230: 2240–2251, 2015. © 2015 Wiley Periodicals, Inc.