title: Targeting renal cancer with a combination of WNT inhibitors and a bi-functional peptide.
abstract: OBJECTIVE
  Advanced renal cancer has still a very poor prognosis. We combined wingless-related integration site (WNT) inhibitors with a bi-functional peptide, as previous research has proven their individual efficacy in cancer therapy. Each targets cancer cells differently. We wanted to determine whether they have an additive effect.
  
  
  METHODS
  Our bi-functional peptide consists of a target domain (LTVSPWY) and a lytic domain (KLAKLAK)2. We used three WNT inhibitors: Ethacrinic acid, ciclopirox olamine, piroctone olamine and combined each with the bi-functional peptide. They were tested on three different renal cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay.
  
  
  RESULTS
  We demonstrated a synergistic effect of WNT inhibitors with the bi-functional peptide. The vitality of cancer cells was reduced significantly (p<0.05), while healthy cells were mostly unaffected.
  
  
  CONCLUSIONS
  The combination of WNT inhibitor and the bi-functional peptide may lead to new treatment options as toxic side-effects can be reduced due to the lower doses of agent required.
authors.affiliation: Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, 53105 Bonn, Germany. Ingo.Schmidt-Wolf@ukb.uni-bonn.de
authors.forename: Christiane M
authors.initials: CM
authors.lastname: Koller
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077768:Ciclopirox; D004338:Drug Combinations; D004976:Ethacrynic Acid / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011728:Pyridones / Q000494:pharmacology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D004983:Ethanolamines; D009842:Oligopeptides; D010455:Peptides; D011728:Pyridones; D051153:Wnt Proteins; C576676:leucyl-threonyl-valyl-seryl-prolyl-tryptophyl-tyrosine; D000077768:Ciclopirox; C052599:piroctone olamine; D004976:Ethacrynic Acid
keywords: Renal cancer; WNT inhibitors; bi-functional peptide; targeted therapy