title: Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination.
abstract: OBJECTIVE
  To investigate the effects of E7080 and N (5)-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO) on colorectal cancer alone and in combination.
  
  
  METHODS
  HT29 colorectal cancer cell line from Sap Institute was used. Real-time cell analysis (xCELLigence system) was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation. While apoptosis was determined with Annexin V staining, and the effect of agents on angiogenesis was determined with chorioallantoic membrane (CAM) model.
  
  
  RESULTS
  We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration (IC50) value of 5.60×10(-8) mol/L. Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Antiangiogenic scores of E7080 were 1.2, 1.0 and 0.6 for 100, 10 and 1 nmol/L E7080 concentrations, respectively. Furthermore, apoptosis has been detected in 71% of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect. Meanwhile administration of L-NIO alone did not show any effect, but the combination of E7080 with L-NIO increased the antiproliferative, antiangiogenic and apoptotic effects of E7080.
  
  
  CONCLUSIONS
  Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors. Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080.
authors.affiliation: Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas 58140, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Altun
authors.forename: Tijen Kaya
authors.initials: TK
authors.lastname: Temiz
authors.forename: Ezgi
authors.initials: E
authors.lastname: Balcı
authors.forename: Zübeyde Akın
authors.initials: ZA
authors.lastname: Polat
authors.forename: Mustafa
authors.initials: M
authors.lastname: Turan
keywords: E7080; N5-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO); colorectal cancer; tyrosine kinase (TK); xCELLigence system