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.