Natural and redesigned wasp venom peptides with selective antitumoral activity

Autor(es)

Torres, Marcelo D. T. ^{[1, 2, 3, 4]} ; Andrade, Gislaine P. ^[1] ; Sato, Roseli H. ^[1] ; Pedron, Cibele N. ^[1] ; Manieri, Tania M. ^[1] ; Cerchiaro, Giselle ^[1] ; Ribeiro, Anderson O. ^[1] ; de la Fuente-Nunez, Cesar ^{[2, 3, 4]} ; Oliveira, Jr., Vani X. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[2] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 - USA

^[3] MIT, Elect Res Lab, Dept Biol Engn, Synthet Biol Grp, MIT Synthet Biol Ctr, Cambridge, MA 02139 - USA

^[4] Broad Inst MIT & Harvard, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 - USA

• Tipo de documento: Artigo Científico
• Fonte: Beilstein Journal of Organic Chemistry; v. 14, p. 1693-1703, JUL 6 2018.
• Citações Web of Science: 8

Resumo

About 1 in 8 U.S. women (approximate to 12%) will develop invasive breast cancer over the course of their lifetime. Surgery, chemotherapy, radiotherapy, and hormone manipulation constitute the major treatment options for breast cancer. Here, we show that both a natural antimicrobial peptide (AMP) derived from wasp venom (decoralin, Dec-NH2), and its synthetic variants generated via peptide design, display potent activity against cancer cells. We tested the derivatives at increasing doses and observed anticancer activity at concentrations as low as 12.5 mu mol L-1 for the selective targeting of MCF-7 breast cancer cells. Flow cytometry assays further revealed that treatment with wild-type (WT) peptide Dec-NH2 led to necrosis of MCF-7 cells. Additional atomic force microscopy (AFM) measurements indicated that the roughness of cancer cell membranes increased significantly when treated with lead peptides compared to controls. Biophysical features such as helicity, hydrophobicity, and net positive charge were identified to play an important role in the anticancer activity of the peptides. Indeed, abrupt changes in peptide hydrophobicity and conformational propensity led to peptide inactivation, whereas increasing the net positive charge of peptides enhanced their activity. We present peptide templates with selective activity towards breast cancer cells that leave normal cells unaffected. These templates represent excellent scaffolds for the design of selective anticancer peptide therapeutics. (AU)

• Processo FAPESP: 14/18527-8 - Ftalocianinas e Naftalocianinas: síntese de macrociclos anfifílicos para aplicação em Terapia Fotodinâmica
• Beneficiário: Anderson Orzari Ribeiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/09652-9 - Danos a biomoléculas em sistema celular neuronal com desbalanço redox e metálico
• Beneficiário: Giselle Cerchiaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/12938-6 - Peptídeos biologicamente ativos em micro-organismos patogênicos
• Beneficiário: Vani Xavier de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/04507-5 - Aplicações biológicas de novos peptídeos antimicrobianos
• Beneficiário: Marcelo Der Torossian Torres
• Modalidade de apoio: Bolsas no Brasil - Doutorado