Natural and redesigned wasp venom peptides with selective antitumoral activity
About 1 in 8 U.S. women (≈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 was...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2018-07-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.14.144 |
| _version_ | 1818963103479496704 |
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| author | Marcelo D. T. Torres Gislaine P. Andrade Roseli H. Sato Cibele N. Pedron Tania M. Manieri Giselle Cerchiaro Anderson O. Ribeiro Cesar de la Fuente-Nunez Vani X. Oliveira Jr. |
| author_facet | Marcelo D. T. Torres Gislaine P. Andrade Roseli H. Sato Cibele N. Pedron Tania M. Manieri Giselle Cerchiaro Anderson O. Ribeiro Cesar de la Fuente-Nunez Vani X. Oliveira Jr. |
| author_sort | Marcelo D. T. Torres |
| collection | DOAJ |
| description | About 1 in 8 U.S. women (≈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 μmol 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. |
| first_indexed | 2024-12-20T12:39:54Z |
| format | Article |
| id | doaj.art-de30769225a843559aa99043f1d7aa35 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-20T12:39:54Z |
| publishDate | 2018-07-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-de30769225a843559aa99043f1d7aa352022-12-21T19:40:31ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972018-07-011411693170310.3762/bjoc.14.1441860-5397-14-144Natural and redesigned wasp venom peptides with selective antitumoral activityMarcelo D. T. Torres0Gislaine P. Andrade1Roseli H. Sato2Cibele N. Pedron3Tania M. Manieri4Giselle Cerchiaro5Anderson O. Ribeiro6Cesar de la Fuente-Nunez7Vani X. Oliveira Jr.8Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilSynthetic Biology Group, MIT Synthetic Biology Center, Research Laboratory of Electronics, Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology; Broad Institute of MIT and Harvard, The Center for Microbiome Informatics and Therapeutics, Cambridge, 02139, MA, United States of AmericaCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, BrazilAbout 1 in 8 U.S. women (≈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 μmol 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.https://doi.org/10.3762/bjoc.14.144breast cancerdecoralinMCF-7 cellspeptide designselective anticancer peptidesstructure–activity relationships |
| spellingShingle | Marcelo D. T. Torres Gislaine P. Andrade Roseli H. Sato Cibele N. Pedron Tania M. Manieri Giselle Cerchiaro Anderson O. Ribeiro Cesar de la Fuente-Nunez Vani X. Oliveira Jr. Natural and redesigned wasp venom peptides with selective antitumoral activity Beilstein Journal of Organic Chemistry breast cancer decoralin MCF-7 cells peptide design selective anticancer peptides structure–activity relationships |
| title | Natural and redesigned wasp venom peptides with selective antitumoral activity |
| title_full | Natural and redesigned wasp venom peptides with selective antitumoral activity |
| title_fullStr | Natural and redesigned wasp venom peptides with selective antitumoral activity |
| title_full_unstemmed | Natural and redesigned wasp venom peptides with selective antitumoral activity |
| title_short | Natural and redesigned wasp venom peptides with selective antitumoral activity |
| title_sort | natural and redesigned wasp venom peptides with selective antitumoral activity |
| topic | breast cancer decoralin MCF-7 cells peptide design selective anticancer peptides structure–activity relationships |
| url | https://doi.org/10.3762/bjoc.14.144 |
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