Cargando…

Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin

A recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, induces apoptosis in cultured tumor cells. The tumor suppression efficacy of RL2 was shown against mouse hepatoma-1 cells and MDA-MB-231 human breast adenocarcinoma cells. The RL2-based therapeutic drug lactaptin is dist...

Descripción completa

Detalles Bibliográficos
Autores principales: Nemudraya, Anna A., Makartsova, Anna A., Fomin, Alexandr S., Nushtaeva, Anna A., Koval, Olga A., Richter, Vladimir A., Kuligina, Elena V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981335/
https://www.ncbi.nlm.nih.gov/pubmed/27513518
http://dx.doi.org/10.1371/journal.pone.0160980
_version_ 1782447594781278208
author Nemudraya, Anna A.
Makartsova, Anna A.
Fomin, Alexandr S.
Nushtaeva, Anna A.
Koval, Olga A.
Richter, Vladimir A.
Kuligina, Elena V.
author_facet Nemudraya, Anna A.
Makartsova, Anna A.
Fomin, Alexandr S.
Nushtaeva, Anna A.
Koval, Olga A.
Richter, Vladimir A.
Kuligina, Elena V.
author_sort Nemudraya, Anna A.
collection PubMed
description A recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, induces apoptosis in cultured tumor cells. The tumor suppression efficacy of RL2 was shown against mouse hepatoma-1 cells and MDA-MB-231 human breast adenocarcinoma cells. The RL2-based therapeutic drug lactaptin is distributed evenly throughout the organism, which reduces its antitumor efficacy. In the current study, we obtained a genetic construct that allows production of the recombinant fusion protein T3-RL2, consisting of RL2 and T3 peptide (YTYDPWLIFPAN), in E. coli cells. T3 peptide was selected from a phage peptide library as a result of two screenings: in vitro using MDA-MB-231 cell culture and in vivo using a mouse xenograft model of breast cancer MDA-MB-231. It was shown that the displayed peptide T3 provides binding and internalization of phage particles by MDA-MB-231 cells and their specific accumulation in MDA-MB-231 tumor tissue. In addition, based on the nucleotide sequences coding RL2 and the known tumor-targeting peptide iRGD, we obtained genetic constructs that provide synthesis of fusion proteins RL2-iRGD and RL-iRGD-His. We studied the cytotoxic activity of fusion proteins T3-RL2, RL2-iRGD and RL-iRGD-His in vitro using MDA-MB-231 and MCF-7 human adenocarcinoma cells. The in vitro results showed that the fusion proteins inhibit proliferation of both cell cultures, and their cytotoxic activity is higher than that of RL2. In vivo experiments on the study of the antitumor efficacy of the obtained fusion proteins demonstrated that T3-RL2 protein significantly inhibits MDA-MB-231 tumor growth in a xenograft model compared with RL2, while the antitumor effect of RL2-iRGD and RL-iRGD-His proteins is comparable to the effect of RL2.
format Online
Article
Text
id pubmed-4981335
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-49813352016-08-29 Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin Nemudraya, Anna A. Makartsova, Anna A. Fomin, Alexandr S. Nushtaeva, Anna A. Koval, Olga A. Richter, Vladimir A. Kuligina, Elena V. PLoS One Research Article A recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, induces apoptosis in cultured tumor cells. The tumor suppression efficacy of RL2 was shown against mouse hepatoma-1 cells and MDA-MB-231 human breast adenocarcinoma cells. The RL2-based therapeutic drug lactaptin is distributed evenly throughout the organism, which reduces its antitumor efficacy. In the current study, we obtained a genetic construct that allows production of the recombinant fusion protein T3-RL2, consisting of RL2 and T3 peptide (YTYDPWLIFPAN), in E. coli cells. T3 peptide was selected from a phage peptide library as a result of two screenings: in vitro using MDA-MB-231 cell culture and in vivo using a mouse xenograft model of breast cancer MDA-MB-231. It was shown that the displayed peptide T3 provides binding and internalization of phage particles by MDA-MB-231 cells and their specific accumulation in MDA-MB-231 tumor tissue. In addition, based on the nucleotide sequences coding RL2 and the known tumor-targeting peptide iRGD, we obtained genetic constructs that provide synthesis of fusion proteins RL2-iRGD and RL-iRGD-His. We studied the cytotoxic activity of fusion proteins T3-RL2, RL2-iRGD and RL-iRGD-His in vitro using MDA-MB-231 and MCF-7 human adenocarcinoma cells. The in vitro results showed that the fusion proteins inhibit proliferation of both cell cultures, and their cytotoxic activity is higher than that of RL2. In vivo experiments on the study of the antitumor efficacy of the obtained fusion proteins demonstrated that T3-RL2 protein significantly inhibits MDA-MB-231 tumor growth in a xenograft model compared with RL2, while the antitumor effect of RL2-iRGD and RL-iRGD-His proteins is comparable to the effect of RL2. Public Library of Science 2016-08-11 /pmc/articles/PMC4981335/ /pubmed/27513518 http://dx.doi.org/10.1371/journal.pone.0160980 Text en © 2016 Nemudraya et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nemudraya, Anna A.
Makartsova, Anna A.
Fomin, Alexandr S.
Nushtaeva, Anna A.
Koval, Olga A.
Richter, Vladimir A.
Kuligina, Elena V.
Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin
title Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin
title_full Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin
title_fullStr Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin
title_full_unstemmed Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin
title_short Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin
title_sort tumor-specific peptide, selected from a phage peptide library, enhances antitumor activity of lactaptin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981335/
https://www.ncbi.nlm.nih.gov/pubmed/27513518
http://dx.doi.org/10.1371/journal.pone.0160980
work_keys_str_mv AT nemudrayaannaa tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin
AT makartsovaannaa tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin
AT fominalexandrs tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin
AT nushtaevaannaa tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin
AT kovalolgaa tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin
AT richtervladimira tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin
AT kuliginaelenav tumorspecificpeptideselectedfromaphagepeptidelibraryenhancesantitumoractivityoflactaptin