title: Growth of HepG2 cells was suppressed through modulation of STAT6/IL-4 and IL-10 in RAW 264.7 cells treated by phytoglycoprotein (38 kDa).
abstract: Macrophage type 2 (M2) is closely associated with tumor progression and metastasis. Thus, in this study, the antitumor effect of Styrax japonica Siebold et al. Zuccarini (SJSZ) glycoprotein on HepG2 cell proliferation through modulating M2 was investigated by measuring [³H]-thymidine incorporation and proliferating cell nuclear antigen (PCNA), nitric oxide (NO), reactive oxygen species (ROS), mitogen-activated protein kinases, signal transducer and activator of transcription (STAT) 6, cytokines [interleukin (IL)-4, IL-10, IL-12, and interferon (IFN)-γ], and CD163-positive cells using biochemical analysis, radioactivity, Western blot, ELISA, quantitative real-time polymerase chain reaction, and flow cytometry in coculture system. RAW 264.7 cells were found to be cytotoxic to HepG2 cells but [³H]-thymidine incorporation and expression of PCNA was suppressed in the presence of the SJSZ glycoprotein (20 μg/ml). The SJSZ glycoprotein normalized production of NO and ROS and expression of inducible nitric oxide synthase, IFN-γ, and IL-12 but suppressed expression of pSTAT6, IL-4, IL-10, and CD163-positive cells. Thus, the results of this study suggest that the SJSZ glycoprotein suppresses proliferation of HepG2 cells by modulating M2.
authors.affiliation: Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology-BK21, Chonnam National University, 300 Yongbong-Dong, Gwangju 500-757, South Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Kye-Taek
authors.initials: KT
authors.lastname: Lim
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D006023:Glycoproteins / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010940:Plant Proteins / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D050800:STAT6 Transcription Factor / Q000096:biosynthesis; D032362:Styrax; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006023:Glycoproteins; D015850:Interleukin-6; D010940:Plant Proteins; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases