title: Cudrania tricupidata bureau (CTB) glycoprotein inhibits proliferation by Di(2-ethylhexyl) phthalate in primary splenocytes: responses in cell proliferation signaling.
abstract: The aim of the present study was to evaluate inhibitory effect of CTB glycoprotein isolated from Cudrania tricuspidata Bureau on DEHP-induced cell proliferation in lymphocytes. Our results revealed that DEHP increased lymphocyte proliferation as confirmed by increasing [(3)H]thymidine incorporation, and proliferating cell nuclear antigen (PCNA), cyclin D1, and cyclin-dependent kinase (CDK)-4 expression. This was accompanied by induced intracellular Ca(2+) level, protein kinase C (PKC) translocation from cytosol to membrane, ERK1/2 phosphorylation, and nuclear factor (NF)-κB transcriptional activation in DEHP-treated cells. However, CTB glycoprotein (100 μg/ml) reduced labeled thymidine incorporation and PCNA expression in DEHP-treated cells. Additionally CTB glycoprotein reduced Ca(2+) level, PKC translocation, ERK1/2 phosphorylation, NF-κB transcriptional activation, cell cycle proteins (cyclin D1 and CDK4) expression in cells. The activation of NF-κB was collectively blocked by pretreatment with PKC inhibitor (staurosporine) and ERK1/2 inhibitor (PD98059), respectively. The results from these experiments indicate that CTB glycoprotein inhibits cell proliferation via down regulations of Ca(2+)/PKC, ERK1/2, and cell cycle proteins induced by DEHP. Therefore, we suggest that the CTB glycoprotein might be one component for prevention of cell proliferation-related immune diseases.
authors.affiliation: Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology (BK21), Chonnam National University, Gwang-ju 500-757, 500-757, South Korea.
authors.forename: Phil-Sun
authors.initials: PS
authors.lastname: Oh
authors.forename: Kye-Taek
authors.initials: KT
authors.lastname: Lim
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D015536:Down-Regulation; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D029586:Moraceae / Q000737:chemistry*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000166:cytology
chemical_list: D018797:Cell Cycle Proteins; D006023:Glycoproteins; D004051:Diethylhexyl Phthalate; D011493:Protein Kinase C; D002118:Calcium