title: Baicalein reduces the invasion of glioma cells via reducing the activity of p38 signaling pathway.
abstract: Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s) in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin) could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma.
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Jianrui
authors.initials: J
authors.lastname: Lv
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lei
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Meng
authors.affiliation: Anesthesia Department, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Xue
authors.affiliation: National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, Xi'an Jiaotong University, Xi'an, P. R. China ; Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China ; General Surgeon Department of Cadre's Ward, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004357:Drug Synergism; D044950:Flavanones / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D031364:Scutellaria baicalensis / Q000737:chemistry; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D007093:Imidazoles; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C499814:Scutellaria baicalensis extract; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C006680:baicalein; D000841:Anisomycin; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C093642:SB 203580