title: Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition by suppressing cyclin D1 expression and matrix-metalloproteinase-2 activity in human lung cancer cells.
abstract: OBJECTIVE
  Scutellaria baicalensis Georgi is a widely used medicinal herb in several Asian countries including Korea. The various medicinal properties attributed to Scutellaria baicalensis include anti-bacterial, anti-viral, anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of Scutellaria baicalensis water extract (SBWE) on A549 non-small-cell-lung cancer cells and the A549 expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and matrix metalloproteinase-2 (MMP-2), and the effects of SBWE on cell cycle progression, especially the G1/S phase, and on cell motility.
  
  
  METHODS
  SBWE cytotoxicity was assessed by a standard colorimetric assay utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and expression of cyclin D1 and CDK4 protein in SBWE-treated A549 cells was assessed by Western blot analysis. Flow cytometry analysis was performed to determine the effect of SBWE on A549 cell cycle progression. A549 cell MMP-2 activity was examined by zymography. Cell motility and migration was assessed by a scratch wound healing assay.
  
  
  RESULTS
  SBWE was not cytotoxic. The production of Cyclin D1, CDK4 and MMP-2 activity were significantly decreased in a SBWE dose-dependent manner, with maximum inhibition occurring at SBWE concentrations of 250 μg/ml and 500 μg/ml. SBWE inhibited cell cycle progression in the G1/S phase and significantly inhibited the motility of A549 cells.
  
  
  CONCLUSIONS
  Cyclin D1 protein may be associated with MMP-2 activity and cell motility. Thus, SBWE promotes a strong protective effect against MMP-2 mediated metastasis and cell proliferation through the down-regulation of cyclin D1. SBWE may be a useful chemotherapeutic agent for lung cancer.
authors.affiliation: Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Park
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Sang-Rim
authors.initials: SR
authors.lastname: Kang
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.forename: Do-Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Han
authors.forename: Gon-Sup
authors.initials: GS
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D020834:Ethnopharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D055670:Medicine, Korean Traditional; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D056910:Republic of Korea; D031364:Scutellaria baicalensis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C530104:CCND1 protein, human; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; C499814:Scutellaria baicalensis extract; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2