The CT20 peptide: More than a Piece of Bax

Abstract

Use of cytotoxic peptides for cancer treatment is an emerging therapeutic direction with promising potential; however, in many instances the intracellular actions of these peptides remain unknown. Finding ways to systematically decipher the intercellular targets and functions of rationally designed or endogenously sourced therapeutic peptides to better define clinical use is a significant challenge that needs to be addressed. Here we describe our recent results outlining the activity of CT20p, a peptide derived from the pro-apoptotic protein Bax, which specifically kills metastatic cancer cells but not normal epithelial cells. Using breast cancer as a model system to test the peptide, we found that CT20p can be delivered to cells by polymeric hyper branched nanoparticles and that, once intracellular, have profound effects on cytosolic proteins and organelles in a cancerspecific fashion that are different from the parent protein. In cancer cells, CT20p localizes to the mitochondria, forms pores in mitochondrial-like membranes, alters mitochondrial movement and membrane polarization, and impairs cytoskeletal reorganization, leading to cell detachment and death. Further, we discuss our strategy for determining the molecular actions of CT20p that could help inform the activities of other currently available antimicrobial and anticancer therapeutic peptides.