title: Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells.
abstract: BACKGROUND
  Osteopontin (OPN) is one of important molecular targets in cancer progression, metastasis as a calcium-binding, extracellular-matrix-associated protein of the small integrin-binding ligand and, N-linked glycoprotein. In the present study, anti-metastatic mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated on OPN enhanced metastasis in NCI-H460 non- small cell lung cancer cells.
  
  
  METHODS
  Cell viability was measured by MTT assay. Adhesion and invasion assays were carried out to see that EEOS inhibited cell adhesion and invasion in OPN treated and non-treated NCI-H 460 cells. RT-PCR was used to determine the mRNA levels of uPA, uPAR, and EGFR.
  
  
  RESULTS
  EEOS significantly inhibited cell adhesion and invasion in OPN treated and non treated NCI-H460 cells, though EEOS did not show any toxicity up to 200 μg/ml. EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated the expression of CD44 in NCI-H460 cells. In addition, EEOS effectively suppressed the expression of phosphatidylinositide 3-kinases (PI3K) and cyclooxygenase 2 (COX-2) and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells. Also, EEOS significantly attenuated the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and epidermal growth factor receptor (EGFR) at mRNA level and reduced vascular endothelial growth factor (VEGF) production and MMP-9 activity in OPN treated NCI-H460 cells. Furthermore, PI3K/Akt inhibitor LY294002 enhanced anti-metastatic potential of EEOS to attenuate the expression of uPA and MMP-9 in OPN treated NCI-H 460 cells.
  
  
  CONCLUSIONS
  Overall, our findings suggest that anti-metastatic mechanism of EEOS is mediated by inhibition of PI3K/Akt in OPN treated NCI-H460 non-small cell lung cancer cells.
authors.forename: Tae-kyung
authors.initials: TK
authors.lastname: Kwak
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Sunhee
authors.initials: S
authors.lastname: Kim
authors.forename: Gunho
authors.initials: G
authors.lastname: Won
authors.forename: Jeong-Un
authors.initials: JU
authors.lastname: Choi
authors.forename: Kwon
authors.initials: K
authors.lastname: Jeong
authors.forename: Myoungseok
authors.initials: M
authors.lastname: Jeong
authors.forename: Oh Sung
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul 130-701, Republic of Korea. sungkim7@khu.ac.kr.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D018506:Gene Expression Regulation, Plant / Q000187:drug effects; D006801:Humans; D009362:Neoplasm Metastasis; D031339:Ocimum / Q000737:chemistry*; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt