Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells.
camptothecin
cancer
chemotherapy
glioblastoma
niclosamide
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
2022
2022
Historique:
received:
23
02
2022
accepted:
19
04
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
14
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35548329
doi: 10.18632/oncotarget.28227
pii: 28227
pmc: PMC9084225
doi:
Substances chimiques
Antineoplastic Agents
0
Tumor Suppressor Protein p53
0
Niclosamide
8KK8CQ2K8G
DNA Topoisomerases, Type I
EC 5.99.1.2
Camptothecin
XT3Z54Z28A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
642-658Informations de copyright
Copyright: © 2022 Valdez et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.
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