Jump to main content
Jump to site search


Novel cell-penetrating-amyloid peptide conjugates preferentially kill cancer cells

Author affiliations

Abstract

The goal of this study was to develop a peptide which could use the toxic effects of amyloid, a substance which is the hallmark of over 25 known human diseases, to selectively kill cancer cells. Here we demonstrate that two separate amyloid-forming hexapeptides, one from the microtubule associated protein Tau involved in formation of paired helical filaments of Alzheimer's disease, and the other an amyloid forming sequence from apolipoprotein A1, when conjugated to a cell penetrating peptide (CPP) sequence, form toxic oligomers which are stable for up to 14 h and able to enter cells by a combination of endocytosis and transduction. The amyloid peptide conjugates showed selective cytotoxicity to breast cancer, neuroblastoma and cervical cancer cells in culture compared to normal cells. Fluorescence imaging experiments showed the CPP–amyloid peptide oligomers formed intracellular fibrous amyloid, visible in the endosomes/lysosomes, cytosol and nucleus with thioflavin S (ThS) staining. Further experiments with rhodamine-conjugated Dextran, propidium iodide (PI), and acridine orange (AO) suggested the mechanism of cell death was the permeability of the lysosomal membrane brought about by the formation of amyloid pores. Cytotoxicity could be abrogated by inhibitors of lysosomal hydrolases, consistent with a model where lysosomal hydrolases leak into the cytosol and induce cytotoxicity in subsequent downstream steps. Taken together, our data suggest that CPP–amyloid peptide conjugates show potential as a new class of anti-cancer peptides (ACPs).

Graphical abstract: Novel cell-penetrating-amyloid peptide conjugates preferentially kill cancer cells

Back to tab navigation

Publication details

The article was received on 26 Jun 2017, accepted on 09 Sep 2017 and first published on 05 Dec 2017


Article type: Research Article
DOI: 10.1039/C7MD00321H
Citation: Med. Chem. Commun., 2018, Advance Article
  •   Request permissions

    Novel cell-penetrating-amyloid peptide conjugates preferentially kill cancer cells

    J. R. Veloria, L. Chen, L. Li, G. A. M. Breen, J. Lee and W. J. Goux, Med. Chem. Commun., 2018, Advance Article , DOI: 10.1039/C7MD00321H

Search articles by author

Spotlight

Advertisements