Cargando…
Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles
PURPOSE: This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). MATERIALS AND METHODS: Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Yonsei University College of Medicine
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536400/ https://www.ncbi.nlm.nih.gov/pubmed/31124333 http://dx.doi.org/10.3349/ymj.2019.60.6.509 |
_version_ | 1783421732442341376 |
---|---|
author | Jeon, Hyeon Jun Choi, Byul Bo Ra Park, Kwang Ha Hwang, Dae Seok Kim, Uk Kyu Kim, Gyoo Cheon |
author_facet | Jeon, Hyeon Jun Choi, Byul Bo Ra Park, Kwang Ha Hwang, Dae Seok Kim, Uk Kyu Kim, Gyoo Cheon |
author_sort | Jeon, Hyeon Jun |
collection | PubMed |
description | PURPOSE: This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). MATERIALS AND METHODS: Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by WST-1 assay, Hemacolor staining, Hoechst staining, immunofluorescence staining, fluorescence-activated cell sorting analysis, and Western blotting. RESULTS: G361 cells treated with GNP-HER2 showed condensation of nuclei, which is an apoptotic phenomenon, and translocation of apoptosis-inducing factor and cytochrome c from mitochondria into the nucleus and cytoplasm, respectively. Increases in BAX in cells undergoing apoptosis, activation of caspase-3 and -9, and fragmentation of poly (ADP-ribose) polymerase and DNA fragmentation factor 45 (inhibitor of caspase-activated DNase) were observed upon GNP-HER2 treatment. Following GNP-HER2 treatment, an increase of cells in sub-G1 phase, which is a signal of cell apoptosis, was observed. This resulted in the down-regulation of cyclin A, cyclin D1, cyclin E, cdk2, cdk4, and cdc2 and the up-regulation of p21. Thus, GNP-HER2 treatment was confirmed to induce the cessation of cell cycle progression. Also, decreases in phospho-focal adhesion kinase and phospho-human epidermal growth factor receptor, which activate cellular focal adhesion, and decreases in phospho-paxillin, which stimulates the disassembly of filamentous actin, were observed. Reduced cell adhesion and disassembly of the intracellular structure indicated cell deactivation. CONCLUSION: GNP-HER2 can selectively kill G361 melanoma cells without affecting normal cells. The mechanism of G361 cell death upon treatment with GNP-HER2 was apoptosis accompanied by activation of caspases. |
format | Online Article Text |
id | pubmed-6536400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Yonsei University College of Medicine |
record_format | MEDLINE/PubMed |
spelling | pubmed-65364002019-06-04 Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles Jeon, Hyeon Jun Choi, Byul Bo Ra Park, Kwang Ha Hwang, Dae Seok Kim, Uk Kyu Kim, Gyoo Cheon Yonsei Med J Original Article PURPOSE: This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). MATERIALS AND METHODS: Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by WST-1 assay, Hemacolor staining, Hoechst staining, immunofluorescence staining, fluorescence-activated cell sorting analysis, and Western blotting. RESULTS: G361 cells treated with GNP-HER2 showed condensation of nuclei, which is an apoptotic phenomenon, and translocation of apoptosis-inducing factor and cytochrome c from mitochondria into the nucleus and cytoplasm, respectively. Increases in BAX in cells undergoing apoptosis, activation of caspase-3 and -9, and fragmentation of poly (ADP-ribose) polymerase and DNA fragmentation factor 45 (inhibitor of caspase-activated DNase) were observed upon GNP-HER2 treatment. Following GNP-HER2 treatment, an increase of cells in sub-G1 phase, which is a signal of cell apoptosis, was observed. This resulted in the down-regulation of cyclin A, cyclin D1, cyclin E, cdk2, cdk4, and cdc2 and the up-regulation of p21. Thus, GNP-HER2 treatment was confirmed to induce the cessation of cell cycle progression. Also, decreases in phospho-focal adhesion kinase and phospho-human epidermal growth factor receptor, which activate cellular focal adhesion, and decreases in phospho-paxillin, which stimulates the disassembly of filamentous actin, were observed. Reduced cell adhesion and disassembly of the intracellular structure indicated cell deactivation. CONCLUSION: GNP-HER2 can selectively kill G361 melanoma cells without affecting normal cells. The mechanism of G361 cell death upon treatment with GNP-HER2 was apoptosis accompanied by activation of caspases. Yonsei University College of Medicine 2019-06-01 2019-05-22 /pmc/articles/PMC6536400/ /pubmed/31124333 http://dx.doi.org/10.3349/ymj.2019.60.6.509 Text en © Copyright: Yonsei University College of Medicine 2019 https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Jeon, Hyeon Jun Choi, Byul Bo Ra Park, Kwang Ha Hwang, Dae Seok Kim, Uk Kyu Kim, Gyoo Cheon Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles |
title | Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles |
title_full | Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles |
title_fullStr | Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles |
title_full_unstemmed | Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles |
title_short | Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles |
title_sort | induction of melanoma cell-selective apoptosis using anti-her2 antibody-conjugated gold nanoparticles |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536400/ https://www.ncbi.nlm.nih.gov/pubmed/31124333 http://dx.doi.org/10.3349/ymj.2019.60.6.509 |
work_keys_str_mv | AT jeonhyeonjun inductionofmelanomacellselectiveapoptosisusingantiher2antibodyconjugatedgoldnanoparticles AT choibyulbora inductionofmelanomacellselectiveapoptosisusingantiher2antibodyconjugatedgoldnanoparticles AT parkkwangha inductionofmelanomacellselectiveapoptosisusingantiher2antibodyconjugatedgoldnanoparticles AT hwangdaeseok inductionofmelanomacellselectiveapoptosisusingantiher2antibodyconjugatedgoldnanoparticles AT kimukkyu inductionofmelanomacellselectiveapoptosisusingantiher2antibodyconjugatedgoldnanoparticles AT kimgyoocheon inductionofmelanomacellselectiveapoptosisusingantiher2antibodyconjugatedgoldnanoparticles |