Cargando…

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Dong Jin, Jeena, M. T., Kim, Ok-Hee, Hong, Ha-Eun, Seo, Haeyeon, Ryu, Ja-Hyoung, Kim, Say-June
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504046/
https://www.ncbi.nlm.nih.gov/pubmed/32854415
http://dx.doi.org/10.3390/ijms21176126
_version_ 1783584533727150080
author Kim, Dong Jin
Jeena, M. T.
Kim, Ok-Hee
Hong, Ha-Eun
Seo, Haeyeon
Ryu, Ja-Hyoung
Kim, Say-June
author_facet Kim, Dong Jin
Jeena, M. T.
Kim, Ok-Hee
Hong, Ha-Eun
Seo, Haeyeon
Ryu, Ja-Hyoung
Kim, Say-June
author_sort Kim, Dong Jin
collection PubMed
description Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes.
format Online
Article
Text
id pubmed-7504046
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75040462020-09-24 Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer Kim, Dong Jin Jeena, M. T. Kim, Ok-Hee Hong, Ha-Eun Seo, Haeyeon Ryu, Ja-Hyoung Kim, Say-June Int J Mol Sci Article Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes. MDPI 2020-08-25 /pmc/articles/PMC7504046/ /pubmed/32854415 http://dx.doi.org/10.3390/ijms21176126 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Dong Jin
Jeena, M. T.
Kim, Ok-Hee
Hong, Ha-Eun
Seo, Haeyeon
Ryu, Ja-Hyoung
Kim, Say-June
Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer
title Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer
title_full Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer
title_fullStr Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer
title_full_unstemmed Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer
title_short Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer
title_sort novel therapeutic application of self-assembly peptides targeting the mitochondria in in vitro and in vivo experimental models of gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504046/
https://www.ncbi.nlm.nih.gov/pubmed/32854415
http://dx.doi.org/10.3390/ijms21176126
work_keys_str_mv AT kimdongjin noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer
AT jeenamt noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer
AT kimokhee noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer
AT honghaeun noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer
AT seohaeyeon noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer
AT ryujahyoung noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer
AT kimsayjune noveltherapeuticapplicationofselfassemblypeptidestargetingthemitochondriaininvitroandinvivoexperimentalmodelsofgastriccancer