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CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells

Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca(2+) channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases...

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Autores principales: Oliveira-Mendes, Bárbara Bruna Ribeiro de, Horta, Carolina Campolina Rebello, do Carmo, Anderson Oliveira, Biscoto, Gabriela Lago, Sales-Medina, Douglas Ferreira, Leal, Hortênsia Gomes, Brandão-Dias, Pedro Ferreira Pinto, Miranda, Sued Eustáquio Mendes, Aguiar, Carla Jeane, Cardoso, Valbert Nascimento, de Barros, André Luis Branco, Chávez-Olortégui, Carlos, Leite, M. Fátima, Kalapothakis, Evanguedes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170434/
https://www.ncbi.nlm.nih.gov/pubmed/30282983
http://dx.doi.org/10.1038/s41598-018-33133-3
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author Oliveira-Mendes, Bárbara Bruna Ribeiro de
Horta, Carolina Campolina Rebello
do Carmo, Anderson Oliveira
Biscoto, Gabriela Lago
Sales-Medina, Douglas Ferreira
Leal, Hortênsia Gomes
Brandão-Dias, Pedro Ferreira Pinto
Miranda, Sued Eustáquio Mendes
Aguiar, Carla Jeane
Cardoso, Valbert Nascimento
de Barros, André Luis Branco
Chávez-Olortégui, Carlos
Leite, M. Fátima
Kalapothakis, Evanguedes
author_facet Oliveira-Mendes, Bárbara Bruna Ribeiro de
Horta, Carolina Campolina Rebello
do Carmo, Anderson Oliveira
Biscoto, Gabriela Lago
Sales-Medina, Douglas Ferreira
Leal, Hortênsia Gomes
Brandão-Dias, Pedro Ferreira Pinto
Miranda, Sued Eustáquio Mendes
Aguiar, Carla Jeane
Cardoso, Valbert Nascimento
de Barros, André Luis Branco
Chávez-Olortégui, Carlos
Leite, M. Fátima
Kalapothakis, Evanguedes
author_sort Oliveira-Mendes, Bárbara Bruna Ribeiro de
collection PubMed
description Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca(2+) channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca(2+) release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca(2+) active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts’s nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide(14–39) lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca(2+) active toxins and provides new insights into biotechnological applications of animal venoms.
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spelling pubmed-61704342018-10-05 CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells Oliveira-Mendes, Bárbara Bruna Ribeiro de Horta, Carolina Campolina Rebello do Carmo, Anderson Oliveira Biscoto, Gabriela Lago Sales-Medina, Douglas Ferreira Leal, Hortênsia Gomes Brandão-Dias, Pedro Ferreira Pinto Miranda, Sued Eustáquio Mendes Aguiar, Carla Jeane Cardoso, Valbert Nascimento de Barros, André Luis Branco Chávez-Olortégui, Carlos Leite, M. Fátima Kalapothakis, Evanguedes Sci Rep Article Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca(2+) channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca(2+) release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca(2+) active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts’s nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide(14–39) lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca(2+) active toxins and provides new insights into biotechnological applications of animal venoms. Nature Publishing Group UK 2018-10-03 /pmc/articles/PMC6170434/ /pubmed/30282983 http://dx.doi.org/10.1038/s41598-018-33133-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Oliveira-Mendes, Bárbara Bruna Ribeiro de
Horta, Carolina Campolina Rebello
do Carmo, Anderson Oliveira
Biscoto, Gabriela Lago
Sales-Medina, Douglas Ferreira
Leal, Hortênsia Gomes
Brandão-Dias, Pedro Ferreira Pinto
Miranda, Sued Eustáquio Mendes
Aguiar, Carla Jeane
Cardoso, Valbert Nascimento
de Barros, André Luis Branco
Chávez-Olortégui, Carlos
Leite, M. Fátima
Kalapothakis, Evanguedes
CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
title CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
title_full CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
title_fullStr CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
title_full_unstemmed CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
title_short CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
title_sort cpp-ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170434/
https://www.ncbi.nlm.nih.gov/pubmed/30282983
http://dx.doi.org/10.1038/s41598-018-33133-3
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