Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression

Seung-Shick Shin,1,* Dae-Hwa Noh,2,* Byungdoo Hwang,2 Jo-Won Lee,2 Sung Lyea Park,2 Sung-Soo Park,1 Bokyung Moon,2 Wun-Jae Kim,3 Sung-Kwon Moon2 1Department of Food Science and Nutrition, Jeju National University, Jeju, South Korea; 2Department of Food and Nutrition, Chung-Ang University, Anseong,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Shin SS, Noh DH, Hwang B, Lee JW, Park SL, Park SS, Moon B, Kim WJ, Moon SK
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://doaj.org/article/82b9b3b9a27d45fc80f33b0fbe83b241
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:82b9b3b9a27d45fc80f33b0fbe83b241
record_format dspace
spelling oai:doaj.org-article:82b9b3b9a27d45fc80f33b0fbe83b2412021-12-02T01:28:39ZInhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression1178-2013https://doaj.org/article/82b9b3b9a27d45fc80f33b0fbe83b2412018-06-01T00:00:00Zhttps://www.dovepress.com/inhibitory-effect-of-aupt-nss-on-proliferation-migration-and-invasion--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Seung-Shick Shin,1,* Dae-Hwa Noh,2,* Byungdoo Hwang,2 Jo-Won Lee,2 Sung Lyea Park,2 Sung-Soo Park,1 Bokyung Moon,2 Wun-Jae Kim,3 Sung-Kwon Moon2 1Department of Food Science and Nutrition, Jeju National University, Jeju, South Korea; 2Department of Food and Nutrition, Chung-Ang University, Anseong, South Korea; 3Department of Urology, Chungbuk National University, Cheongju, Chungbuk, South Korea *These authors contributed equally to this work Background: Although the diverse biological properties of nanoparticles have been studied intensively, research into their mechanism of action is relatively rare. In this study, we investigated the molecular mechanisms of the anticancer activity of heterometallic Au@Pt-nanoseeds (NSs) against bladder cancers.Materials and methods: Mode of action of Au@Pt-NSs was investigated through MTT assay, flow cytometry analysis, Western immunoblots, real-time qPCR, wound-healing migration and invasion assays, zymography, and electrophoretic mobility shift assay (EMSA).Results: Treatment with Au@Pt-NSs significantly inhibited the proliferation of EJ cells in a dose-dependent manner by inducing G1 phase cell cycle arrest. Among the regulators associated with the G1 cell cycle phase, CDK2, CDK4, cyclin D1, cyclin E, and p21WAF1 were shown to participate in the inhibitory pathways of Au@Pt-NSs. In addition, treatment with Au@Pt-NSs led to upregulation of phospho-p38 MAPK and downregulation of phospho-AKT in EJ cells. Interestingly, Au@Pt-NSs inhibited the migratory and invasive potential of the cells, which was attributed to the suppression of the enzymatic activity of matrix metalloproteinase-9 (MMP-9). Using MMP-9-specific oligonucleotides, we showed that transcription factors such as NF-κB and Sp-1 were responsible for the MMP-9-mediated metastatic potential of EJ cells.Conclusion: Au@Pt-NSs significantly limited the progression, migration, and invasion of bladder cancer EJ cells. Our data represent a novel insight into developing cisplatin-like chemotherapeutic reagents with fewer side effects and provide useful information on molecular markers to monitor patients under Au@Pt-NSs-based chemotherapy. Keywords: nanoseeds, nanomedicine, bladder cancer, molecular mechanismShin SSNoh DHHwang BLee JWPark SLPark SSMoon BKim WJMoon SKDove Medical PressarticleNanoseedsNanomedicineBladder cancerMolecular mechanismMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3295-3310 (2018)
institution DOAJ
collection DOAJ
language EN
topic Nanoseeds
Nanomedicine
Bladder cancer
Molecular mechanism
Medicine (General)
R5-920
spellingShingle Nanoseeds
Nanomedicine
Bladder cancer
Molecular mechanism
Medicine (General)
R5-920
Shin SS
Noh DH
Hwang B
Lee JW
Park SL
Park SS
Moon B
Kim WJ
Moon SK
Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression
description Seung-Shick Shin,1,* Dae-Hwa Noh,2,* Byungdoo Hwang,2 Jo-Won Lee,2 Sung Lyea Park,2 Sung-Soo Park,1 Bokyung Moon,2 Wun-Jae Kim,3 Sung-Kwon Moon2 1Department of Food Science and Nutrition, Jeju National University, Jeju, South Korea; 2Department of Food and Nutrition, Chung-Ang University, Anseong, South Korea; 3Department of Urology, Chungbuk National University, Cheongju, Chungbuk, South Korea *These authors contributed equally to this work Background: Although the diverse biological properties of nanoparticles have been studied intensively, research into their mechanism of action is relatively rare. In this study, we investigated the molecular mechanisms of the anticancer activity of heterometallic Au@Pt-nanoseeds (NSs) against bladder cancers.Materials and methods: Mode of action of Au@Pt-NSs was investigated through MTT assay, flow cytometry analysis, Western immunoblots, real-time qPCR, wound-healing migration and invasion assays, zymography, and electrophoretic mobility shift assay (EMSA).Results: Treatment with Au@Pt-NSs significantly inhibited the proliferation of EJ cells in a dose-dependent manner by inducing G1 phase cell cycle arrest. Among the regulators associated with the G1 cell cycle phase, CDK2, CDK4, cyclin D1, cyclin E, and p21WAF1 were shown to participate in the inhibitory pathways of Au@Pt-NSs. In addition, treatment with Au@Pt-NSs led to upregulation of phospho-p38 MAPK and downregulation of phospho-AKT in EJ cells. Interestingly, Au@Pt-NSs inhibited the migratory and invasive potential of the cells, which was attributed to the suppression of the enzymatic activity of matrix metalloproteinase-9 (MMP-9). Using MMP-9-specific oligonucleotides, we showed that transcription factors such as NF-κB and Sp-1 were responsible for the MMP-9-mediated metastatic potential of EJ cells.Conclusion: Au@Pt-NSs significantly limited the progression, migration, and invasion of bladder cancer EJ cells. Our data represent a novel insight into developing cisplatin-like chemotherapeutic reagents with fewer side effects and provide useful information on molecular markers to monitor patients under Au@Pt-NSs-based chemotherapy. Keywords: nanoseeds, nanomedicine, bladder cancer, molecular mechanism
format article
author Shin SS
Noh DH
Hwang B
Lee JW
Park SL
Park SS
Moon B
Kim WJ
Moon SK
author_facet Shin SS
Noh DH
Hwang B
Lee JW
Park SL
Park SS
Moon B
Kim WJ
Moon SK
author_sort Shin SS
title Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression
title_short Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression
title_full Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression
title_fullStr Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression
title_full_unstemmed Inhibitory effect of Au@Pt-NSs on proliferation, migration, and invasion of EJ bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression
title_sort inhibitory effect of au@pt-nss on proliferation, migration, and invasion of ej bladder carcinoma cells: involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated mmp-9 expression
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/82b9b3b9a27d45fc80f33b0fbe83b241
work_keys_str_mv AT shinss inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT nohdh inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT hwangb inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT leejw inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT parksl inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT parkss inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT moonb inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT kimwj inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
AT moonsk inhibitoryeffectofauptnssonproliferationmigrationandinvasionofejbladdercarcinomacellsinvolvementofcellcycleregulatorssignalingpathwaysandtranscriptionfactormediatedmmp9expression
_version_ 1718403085859028992