title: Apoptotic human neutrophil peptide-1 anti-tumor activity revealed by cellular biomechanics.
abstract: Cancer remains a major cause of morbidity and mortality worldwide. Although progress has been made regarding chemotherapeutic agents, new therapies that combine increased selectivity and efficacy with low resistance are still needed. In the search for new anticancer agents, therapies based on biologically active peptides, in particular, antimicrobial peptides (AMPs), have attracted attention for their decreased resistance development and low cytotoxicity. Many AMPs have proved to be tumoricidal agents against human cancer cells, but their mode of action is still controversial. The existence of common properties shared by the membranes of bacteria and tumor cells points to similar lipid-targeting mechanisms in both cases. On the other hand, anticancer peptides (ACPs) also induce apoptosis and inhibit angiogenesis. Human neutrophil peptide-1 (HNP-1) is an endogenous AMP that has been implicated in different cellular phenomena such as tumor proliferation. The presence of HNP-1 in the serum/plasma of oncologic patients turns this peptide into a potential tumor biomarker. The present work reveals the different effects of HNP-1 on the biophysical and nanomechanical properties of solid and hematological tumor cells. Studies on cellular morphology, cellular stiffness, and membrane ultrastructure and charge using atomic force microscopy (AFM) and zeta potential measurements show a preferential binding of HNP-1 to solid tumor cells from human prostate adenocarcinoma when compared to human leukemia cells. AFM also reveals induction of apoptosis with cellular membrane defects at very low peptide concentrations. Understanding ACPs mode(s) of action will certainly open innovative pathways for drug development in cancer treatment.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal. Electronic address: dianagaspar@fm.ul.pt.
authors.forename: Diana
authors.initials: D
authors.lastname: Gaspar
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal. Electronic address: joaofreire@fm.ul.pt.
authors.forename: João M
authors.initials: JM
authors.lastname: Freire
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal. Electronic address: tr.pacheco@fm.ul.pt.
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Pacheco
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal. Electronic address: joao_barata@fm.ul.pt.
authors.forename: João T
authors.initials: JT
authors.lastname: Barata
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal. Electronic address: macastanho@fm.ul.pt.
authors.forename: Miguel A R B
authors.initials: MA
authors.lastname: Castanho
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001696:Biomechanical Phenomena / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055119:Elastic Modulus / Q000187:drug effects; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force; D011471:Prostatic Neoplasms / Q000473:pathology; D055672:Static Electricity; D023084:alpha-Defensins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D023084:alpha-Defensins; C406413:human neutrophil peptide 1
keywords: Anticancer peptide; Apoptosis; Atomic force microscopy; Membrane charge; Nanomechanical properties; Solid tumor