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Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

[Image: see text] Breast cancer is one of the main causes of premature death in women; current treatments have low selectivity, generating strong physical and psychological sequelae. The palindromic peptide R-1-R (RWQWRWQWR) has cytotoxic activity against different cell lines derived from cancer and...

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Autores principales: Barragán-Cárdenas, Andrea Carolina, Insuasty-Cepeda, Diego Sebastián, Vargas-Casanova, Yerly, López-Meza, Joel Edmundo, Parra-Giraldo, Claudia Marcela, Fierro-Medina, Ricardo, Rivera-Monroy, Zuly Jenny, García-Castañeda, Javier Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850729/
https://www.ncbi.nlm.nih.gov/pubmed/36687035
http://dx.doi.org/10.1021/acsomega.2c07336
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author Barragán-Cárdenas, Andrea Carolina
Insuasty-Cepeda, Diego Sebastián
Vargas-Casanova, Yerly
López-Meza, Joel Edmundo
Parra-Giraldo, Claudia Marcela
Fierro-Medina, Ricardo
Rivera-Monroy, Zuly Jenny
García-Castañeda, Javier Eduardo
author_facet Barragán-Cárdenas, Andrea Carolina
Insuasty-Cepeda, Diego Sebastián
Vargas-Casanova, Yerly
López-Meza, Joel Edmundo
Parra-Giraldo, Claudia Marcela
Fierro-Medina, Ricardo
Rivera-Monroy, Zuly Jenny
García-Castañeda, Javier Eduardo
author_sort Barragán-Cárdenas, Andrea Carolina
collection PubMed
description [Image: see text] Breast cancer is one of the main causes of premature death in women; current treatments have low selectivity, generating strong physical and psychological sequelae. The palindromic peptide R-1-R (RWQWRWQWR) has cytotoxic activity against different cell lines derived from cancer and selectivity against noncancerous cells. To determine if changes in the charge/length of this peptide increase its activity, six peptides were obtained by SPPS, three of them with addition of Arg at the N, C-terminal or both and three with deletion of Arg at the N, C-terminal or both. The cytotoxic and selective activities were evaluated against MCF-7, MDA-MB-231, and MCF-12 cell lines and fibroblast primary cell culture, evidencing that the RR-1-R peptide with the inclusion of Arg in the N-terminal end maintained selectivity and increased cytotoxicity against lines derived from breast cancer. The effect of this addition regarding the type of induced cell death was evaluated by flow cytometry, showing very low rates of necrosis and a significant majority of apoptotic events with activation of both Caspase 8 and Caspase 9. This work allowed us to find a modification that generates a peptide with greater cytotoxic effects and can be considered a promising molecule for other approaches to improve anticancer peptides.
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spelling pubmed-98507292023-01-20 Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines Barragán-Cárdenas, Andrea Carolina Insuasty-Cepeda, Diego Sebastián Vargas-Casanova, Yerly López-Meza, Joel Edmundo Parra-Giraldo, Claudia Marcela Fierro-Medina, Ricardo Rivera-Monroy, Zuly Jenny García-Castañeda, Javier Eduardo ACS Omega [Image: see text] Breast cancer is one of the main causes of premature death in women; current treatments have low selectivity, generating strong physical and psychological sequelae. The palindromic peptide R-1-R (RWQWRWQWR) has cytotoxic activity against different cell lines derived from cancer and selectivity against noncancerous cells. To determine if changes in the charge/length of this peptide increase its activity, six peptides were obtained by SPPS, three of them with addition of Arg at the N, C-terminal or both and three with deletion of Arg at the N, C-terminal or both. The cytotoxic and selective activities were evaluated against MCF-7, MDA-MB-231, and MCF-12 cell lines and fibroblast primary cell culture, evidencing that the RR-1-R peptide with the inclusion of Arg in the N-terminal end maintained selectivity and increased cytotoxicity against lines derived from breast cancer. The effect of this addition regarding the type of induced cell death was evaluated by flow cytometry, showing very low rates of necrosis and a significant majority of apoptotic events with activation of both Caspase 8 and Caspase 9. This work allowed us to find a modification that generates a peptide with greater cytotoxic effects and can be considered a promising molecule for other approaches to improve anticancer peptides. American Chemical Society 2023-01-05 /pmc/articles/PMC9850729/ /pubmed/36687035 http://dx.doi.org/10.1021/acsomega.2c07336 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Barragán-Cárdenas, Andrea Carolina
Insuasty-Cepeda, Diego Sebastián
Vargas-Casanova, Yerly
López-Meza, Joel Edmundo
Parra-Giraldo, Claudia Marcela
Fierro-Medina, Ricardo
Rivera-Monroy, Zuly Jenny
García-Castañeda, Javier Eduardo
Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines
title Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines
title_full Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines
title_fullStr Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines
title_full_unstemmed Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines
title_short Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines
title_sort changes in length and positive charge of palindromic sequence rwqwrwqwr enhance cytotoxic activity against breast cancer cell lines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850729/
https://www.ncbi.nlm.nih.gov/pubmed/36687035
http://dx.doi.org/10.1021/acsomega.2c07336
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