title: 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.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Chou
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kun-Han
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Department of Obstetrics and Gynecology, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: David
authors.initials: D
authors.lastname: Sun
authors.affiliation: Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Hsiu
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pu-Hong
authors.initials: PH
authors.lastname: Kao
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yuh-Lin
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005944:Glucosamine / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D016209:Interleukin-8 / Q000096:biosynthesis*; D061986:MCF-7 Cells; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011493:Protein Kinase C; D005944:Glucosamine