Combinação inovadora de técnicas revela o efeito anticancerígeno de defensina humana em células tumorais

Investigadores portugueses revelaram a actividade anticancerígena de um péptido de origem humana, HNP-1 (human neutrophil peptide-1), sobre células tumorais de próstata e leucemia. Este estudo, recentemente publicado na revista Biochimica et Biophysica Acta – Molecular Cell Research, combina técnicas espectroscópicas com microscopia de força atómica (AFM) para elucidar o mecanismo de acção do péptido anticancerígeno e determinar potenciais fatores responsáveis pela sua actividade selectiva contra células tumorais de próstata. A informação recolhida nesta investigação contribuirá para o desenvolvimento de novas moléculas baseadas em péptidos biologicamente activos que possam ser utilizadas no tratamento de diversos tumores.

Autores e afiliações:

Diana Gaspar, João M. Freire, Teresa R. Pacheco, João T. Barata, Miguel A.R.B. Castanho.

 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal

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.

Revista:

Biochimica et Biophysica Acta – Molecular Cell Research

Link:

http://dx.doi.org/10.1016/j.bbamcr.2014.11.006