Bombesin receptor antagonist BBN/C1-C2 in an in vitro model for colorectal cancer

Colorectal cancer is the third most common cancer and the second most fatal cancer worldwide. One of the strategies for colorectal cancer treatment is targeted peptide therapy that targets certain types of receptors overexpressed on the cell surface. A promising target is a bombesin receptor GRPR, which is abnormally expressed in colorectal cancer. In this paper, we suggest to use BBN/C1-C2 molecule, created on the basis of bombesin, a peptide tropic to GRPR, and knottin, acting as a scaffold to stabilize a molecule, for colorectal cancer treatment. BBN/C1-C2 acts as a GRPR receptor antagonist, which determines BBN/C1-C2 role in the survival of cancer cells. Objective: The aim of the paper is to study the effect of BBN/C1-C2 peptide on colorectal cancer cell survival. Materials and Methods. The effect of BBN/C1-C2 peptide obtained by solid-phase synthesis on cancer cell survival was assessed in HCT-116 culture using fluorescence microscopy (apoptosis, necrosis) and a cell analyzer (cell adhesion dynamics) 3 and 24 hours after exposure. Results: The BBN/C1-C2 peptide (concentrations from 0.2 to 20 μM) was able not only to inhibit cell proliferation, but also to cause cell death (apoptosis) three hours after incubation. Conclusion. BBN/C12-C2 molecule, created on the basis of a GRPR agonist built into a knottin molecule, can be considered as a prototype for a radiopharmaceutical to treat colon tumors.