title: The in vitro antitumor activity of Siegesbeckia glabrescens against ovarian cancer through suppression of receptor tyrosine kinase expression and the signaling pathways.
abstract: Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of a variety of diseases such as allergy, inflammation, acute hepatitis and hypertension. The primary aim of this study was to determine whether the ethanol extract of SG has antitumor activity against ovarian cancer and to identify molecular mechanisms and targets involved in the regulation of cell growth and progression. We demonstrate that SG treatment inhibits proliferation, adhesion, migration and invasion of SKOV-3 human ovarian cancer cells. The anti-proliferative effect of SG on SKOV-3 cells is accompanied by reduced expression of cyclin E and enhanced expression of the cyclin-dependent kinase inhibitor p27(Kip1), leading to inhibition of pRb phosphorylation. We also show that these antitumor activities are found to be mediated through suppression of FAK, ERK, Akt and p70(S6K)-dependent signaling pathways and downregulation of receptor tyrosine kinases such as EGFR, VEGFR-2 and FGFR-1 as well as the cell adhesion molecule N-cadherin. Taken together, our findings suggest further development and evaluation of SG for the treatment of ovarian cancer.
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.forename: Shin Wook
authors.initials: SW
authors.lastname: Choi
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D019659:Asteraceae / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D066246:ErbB Receptors / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D055670:Medicine, Korean Traditional; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D019927:Cyclin E; D010936:Plant Extracts; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; C512478:EGFR protein, human; D066246:ErbB Receptors; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases