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Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation.
- Source :
-
Cancer science [Cancer Sci] 2020 Aug; Vol. 111 (8), pp. 2943-2953. Date of Electronic Publication: 2020 Jun 20. - Publication Year :
- 2020
-
Abstract
- Neuroblastoma (NB) is a childhood malignancy originating from the sympathetic nervous system, and accounts for approximately 15% of all pediatric cancer-related deaths. As the 5-y survival rate of patients with high-risk NB is <50%, novel therapeutic strategies for NB patients are urgently required. Nonaethylene glycol mono('4-iodo-4-biphenyl)ester (9bw) is a polyethylene glycol derivative, synthesized by modifying a compound originally extracted from filamentous bacteria. Although 9bw shows remarkable inhibition of tumor cell growth, the underlying mechanisms remain unclear. Here, we examined the efficacy of 9bw on human NB-derived cells, and investigated the molecular mechanisms underlying the cytotoxic effects of 9bw on these cells. Our results indicated that 9bw induced cell death in NB cells by decreasing the production of ATP. Metabolome analysis and measurement of oxygen consumption indicated that 9bw markedly suppressed oxidative phosphorylation (OXPHOS). Further analyses indicated that 9bw inhibited the activity of mitochondrial respiratory complex I. Moreover, we showed that 9bw inhibited growth of NB in vivo. Based on the results of the present study, 9bw is a good candidate as a novel agent for treatment of NB.<br /> (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Electron Transport Complex I metabolism
Esters chemistry
Esters therapeutic use
Female
Humans
Mice
Mitochondria drug effects
Mitochondria metabolism
Neuroblastoma pathology
Polyethylene Glycols chemistry
Polyethylene Glycols therapeutic use
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Electron Transport Complex I antagonists & inhibitors
Esters pharmacology
Neuroblastoma drug therapy
Oxidative Phosphorylation drug effects
Polyethylene Glycols pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 111
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 32495467
- Full Text :
- https://doi.org/10.1111/cas.14512