title: Inhibitory effect of phytoglycoprotein (38 kDa) on expression of matrix metalloproteinase-9 in 12-O-tetradecanoylphorbol-13-acetate-treated HepG2cells.
abstract: Tumor metastasis is one of the main causes of death for patients with malignant tumors. Matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of various cancer cells. Firstly, glycoprotein isolated from Styrax japonica Siebold et al. Zuccarini (SJSZ) has a molecular weight with 38 kDa and consists of carbohydrate (57.64%) and protein (42.35%). In the composition of SJSZ glycoprotein, carbohydrate mostly consists of glucose (28.17%), galactose (21.85%) and mannose (2.62%) out of 52.64%, respectively. the protein consists of Trp (W, 7.01%), Pro (P, 6.72%), and Ile (I, 5.42%) out of 42.35% as three major amino acids, while total amount of other amino acids is 23.20%. The present study was designed to demonstrate whether or not SJSZ glycoprotein prevents the activity of MMP-9 as a metastasis factor against 12-O-tetradecanoylphorbol-13-acetate (TPA). The study evaluated intracellular ROS and the phosphorylation of mitogen-activated protein kinases (MAPKs: extracellular signal-regulated kinase [ERK], stress-activated protein kinase/c-Jun N-terminal kinase [SAPK/JNK] and the p38 MAPK), the activities of transcriptional factors (nuclear factor [NF]-κB and activator protein [AP]-1), cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and MMP-9 in TPA-induced HepG2 cells using the Western blotting analysis, EMSA and gelatin zymography. The results showed that SJSZ glycoprotein (50 μg/ml) suppressed the production of intracellular ROS and the phosphorylation of ERK, JNK and p38 MAPK, as well as the activities of transcriptional factors (NF-κB and AP-1), COX-2, iNOS, and MMP-9 in TPA-induced HepG2 cells. Taking the aforementioned results into account together, this present study suggested that SJSZ glycoprotein might be a potent anti-metastatic agent that suppresses MMP-9 enzymatic activity via the NF-κB and AP-1 signaling pathway.
authors.affiliation: Molecular Biochemistry Laboratory, Biotechnology Research Institute & Center for the Control of Animal Hazards Using Biotechnology (BK21), Chonnam National University, 300 Yongbong-Dong, Gwang-ju, South Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Kye-Taek
authors.initials: KT
authors.lastname: Lim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D006023:Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D032362:Styrax / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate