Inhibition of PKC-Induced COX-2 and IL-8 Expression in Human Breast Cancer Cells by Glucosamine.

Abstract

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.

• Authors: Wan-Yu Chou, Kun-Han Chuang, David Sun, Yu-Hsiu Lee, Pu-Hong Kao, Yen-Yu Lin, Hsei-Wei Wang, Yuh-Lin Wu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 230 Issue 9 Pg. 2240-51 (Sep 2015) ISSN: 1097-4652 [Electronic] United States
• PMID: 25754990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Interleukin-8
• RNA, Messenger
• Cyclooxygenase 2
• PTGS2 protein, human
• Protein Kinase C
• Glucosamine

Topics

• Animals
• Breast Neoplasms (genetics, pathology)
• Cyclooxygenase 2 (biosynthesis)
• Female
• Gene Expression Regulation, Neoplastic
• Glucosamine (administration & dosage, genetics)
• Humans
• Inflammation (genetics, pathology)
• Interleukin-8 (biosynthesis)
• MCF-7 Cells
• Mice
• Protein Kinase C (metabolism)
• RNA, Messenger (biosynthesis)
• Signal Transduction (drug effects)
• Xenograft Model Antitumor Assays