Targeting Prostate Cancer with a Combination of WNT Inhibitors and a Bi-functional Peptide

Abstract

Background/aim: 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.

Materials and methods: 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.

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

Conclusion: Our findings potentially allow safer treatment since lower concentrations of WNT inhibitors can be used in combination with this bi-functional peptide.

Keywords: Prostate cancer; WNT inhibitors; bi-functional peptide; targeted therapy.