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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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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. |
format | Online Article Text |
id | pubmed-9850729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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