Cargando…

Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells

Glioblastoma multiforme (GBM) is one of the deadliest cancers of the brain. Its ability to infiltrate healthy brain tissues renders it difficult to remove surgically. Furthermore, it exhibits high rates of radio- and chemoresistance, making the survival rates of patients with GBM poor. Therefore, no...

Descripción completa

Detalles Bibliográficos
Autores principales: Valdez, Laura, Cheng, Benxu, Gonzalez, Daniela, Rodriguez, Reanna, Campano, Paola, Tsin, Andrew, Fang, Xiaoqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084225/
https://www.ncbi.nlm.nih.gov/pubmed/35548329
http://dx.doi.org/10.18632/oncotarget.28227
_version_ 1784703565082656768
author Valdez, Laura
Cheng, Benxu
Gonzalez, Daniela
Rodriguez, Reanna
Campano, Paola
Tsin, Andrew
Fang, Xiaoqian
author_facet Valdez, Laura
Cheng, Benxu
Gonzalez, Daniela
Rodriguez, Reanna
Campano, Paola
Tsin, Andrew
Fang, Xiaoqian
author_sort Valdez, Laura
collection PubMed
description Glioblastoma multiforme (GBM) is one of the deadliest cancers of the brain. Its ability to infiltrate healthy brain tissues renders it difficult to remove surgically. Furthermore, it exhibits high rates of radio- and chemoresistance, making the survival rates of patients with GBM poor. Therefore, novel effective therapies for GBM remain urgently in demand. Niclosamide is an anti-helminthic drug and recently it has been receiving attention due to its reported anticancer effects in cancer models, including GBM. Furthermore, camptothecin (CPT) is a naturally-occurring alkaloid and has been previously reported to be a potential chemotherapeutic agent by targeting the nuclear topoisomerase I. In the present study, the possible combined chemotherapeutic effects of niclosamide and CPT on the human glioblastoma cell line U87 MG was investigated by MTT assay and western blot analysis. Niclosamide exhibited synergistic activities with CPT to suppress the proliferation of U87 MG cells. Additionally, niclosamide suppressed cell proliferation and induced cell death mainly by triggering ER stress and autophagy, whilst CPT induced cell apoptosis mainly through p53-mediated mitochondrial dysfunction and activation of the MAPK (ERK/JNK) pathways. Overall, these findings suggest that co-administration of niclosamide and CPT may provide a novel therapeutic treatment strategy for GBM.
format Online
Article
Text
id pubmed-9084225
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-90842252022-05-10 Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells Valdez, Laura Cheng, Benxu Gonzalez, Daniela Rodriguez, Reanna Campano, Paola Tsin, Andrew Fang, Xiaoqian Oncotarget Research Paper Glioblastoma multiforme (GBM) is one of the deadliest cancers of the brain. Its ability to infiltrate healthy brain tissues renders it difficult to remove surgically. Furthermore, it exhibits high rates of radio- and chemoresistance, making the survival rates of patients with GBM poor. Therefore, novel effective therapies for GBM remain urgently in demand. Niclosamide is an anti-helminthic drug and recently it has been receiving attention due to its reported anticancer effects in cancer models, including GBM. Furthermore, camptothecin (CPT) is a naturally-occurring alkaloid and has been previously reported to be a potential chemotherapeutic agent by targeting the nuclear topoisomerase I. In the present study, the possible combined chemotherapeutic effects of niclosamide and CPT on the human glioblastoma cell line U87 MG was investigated by MTT assay and western blot analysis. Niclosamide exhibited synergistic activities with CPT to suppress the proliferation of U87 MG cells. Additionally, niclosamide suppressed cell proliferation and induced cell death mainly by triggering ER stress and autophagy, whilst CPT induced cell apoptosis mainly through p53-mediated mitochondrial dysfunction and activation of the MAPK (ERK/JNK) pathways. Overall, these findings suggest that co-administration of niclosamide and CPT may provide a novel therapeutic treatment strategy for GBM. Impact Journals LLC 2022-05-05 /pmc/articles/PMC9084225/ /pubmed/35548329 http://dx.doi.org/10.18632/oncotarget.28227 Text en Copyright: © 2022 Valdez et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Valdez, Laura
Cheng, Benxu
Gonzalez, Daniela
Rodriguez, Reanna
Campano, Paola
Tsin, Andrew
Fang, Xiaoqian
Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells
title Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells
title_full Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells
title_fullStr Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells
title_full_unstemmed Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells
title_short Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells
title_sort combined treatment with niclosamide and camptothecin enhances anticancer effect in u87 mg human glioblastoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084225/
https://www.ncbi.nlm.nih.gov/pubmed/35548329
http://dx.doi.org/10.18632/oncotarget.28227
work_keys_str_mv AT valdezlaura combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells
AT chengbenxu combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells
AT gonzalezdaniela combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells
AT rodriguezreanna combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells
AT campanopaola combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells
AT tsinandrew combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells
AT fangxiaoqian combinedtreatmentwithniclosamideandcamptothecinenhancesanticancereffectinu87mghumanglioblastomacells