Targeting Prostate Cancer with a Combination of WNT Inhibitors and a Bi-functional Peptide.
Prostate cancer is the most common cancer in the Western world. A bi-functional peptide was combined with wingless-related integration site (WNT) inhibitors to determine if there is an additive therapeutic effect when they are used against prostate cancer, since their efficacy has already been proven when used alone.



A bi-functional peptide (TP-LYT) was designed with a target domain (LTVSPWY) and a lytic domain (KLAKLAK)2, and a second peptide with the same lytic domain but a random sequence instead of the target domain was used as a negative control. Two different WNT inhibitors were used, ethacrynic acid and ciclopiroxolamine. They were tested on prostate cancer cells using the WST-8 assay.



A synergistic effect of peptides and WNT inhibitors was demonstrated, increasing the toxicity against cancer cells.



Our findings potentially allow safer treatment since lower concentrations of WNT inhibitors can be used in combination with this bi-functional peptide.
Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital Bonn, Rheinische Friedrich Wilhelm University Bonn, Bonn, Germany.|Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany.
Calogero S
CS
Messina
Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany.
Hans
H
Weiher
Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital Bonn, Rheinische Friedrich Wilhelm University Bonn, Bonn, Germany Ingo.Schmidt-Wolf@ukb.uni-bonn.de.
Ingo G H
IG
Schmidt-Wolf
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000077768:Ciclopirox; D004357:Drug Synergism; D004976:Ethacrynic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000072417:Protein Domains; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
D036341:Intercellular Signaling Peptides and Proteins; C535058:KLA peptide; D009842:Oligopeptides; D010455:Peptides; D011728:Pyridones; D051153:Wnt Proteins; C576676:leucyl-threonyl-valyl-seryl-prolyl-tryptophyl-tyrosine; D000077768:Ciclopirox; D004976:Ethacrynic Acid
Prostate cancer; WNT inhibitors; bi-functional peptide; targeted therapy