title: Glucosamine, a naturally occurring amino monosaccharide, inhibits A549 and H446 cell proliferation by blocking G1/S transition.
abstract: Uncontrolled proliferation is important in tumorigenesis. In the present study, the effects of glucosamine on lung cancer cell proliferation were investigated. The expression of cyclin E, one of the key cyclins in the G1/S transition, and Skp2, the ubiquitin ligase subunit that targets the negative cell cycle regulator, p27Kip1, were also assessed. Moreover, the underlying mechanisms of action of glucosamine were investigated in lung cancer cells. A549 and H446 cells were synchronized using thymidine in the presence or absence of glucosamine. The effect of glucosamine on lung cancer cell proliferation was determined by MTT assay. Cyclin E and p27Kip1 proteins and their phosphorylation levels were detected by western blot analysis. Furthermore, the effect of glucosamine on the cell cycle was evaluated by flow cytometry. Glucosamine was found to inhibit lung cancer cell proliferation and to suppress Skp2 and cyclin E expression. Notably, the phosphorylation levels of cyclin E (Thr62) and p27Kip1 (Thr187) were downregulated by glucosamine, and negatively correlated with degradation. Glucosamine was also found to arrest lung cancer cells in the G1/S phase. Thus, glucosamine may inhibit lung cancer cell proliferation by blocking G1/S transition through the inhibition of cyclin E and Skp2 protein expression.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Ju
authors.forename: Aiming
authors.initials: A
authors.lastname: Yu
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Sun
authors.forename: Didi
authors.initials: D
authors.lastname: Wu
authors.forename: Hongkai
authors.initials: H
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005944:Glucosamine / Q000633:toxicity*; D006801:Humans; D015513:Oncogene Proteins; D010766:Phosphorylation; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005944:Glucosamine