Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation. Issue 8 (20th June 2020)

• Record Type: Journal Article
• Authors: Nagasaki‐Maeoka, Eri; Ikeda, Kazuhiro; Takayama, Ken‐ichi; Hirano, Takayuki; Ishizuka, Yoshiaki; Koshinaga, Tsugumichi; Tsukune, Naoya; Takayama, Tadateru; Inoue, Satoshi; Fujiwara, Kyoko
• Is Part Of: Cancer science. Volume 111:Issue 8(2020)
• Page Start: 2943
• Page End: 2953
• Publication Date: 2020-06-20
• Subjects: anticancer drug -- mitochondrial respiratory complex I -- neuroblastoma -- oxidative phosphorylation -- polyethylene glycol derivative; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14512
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : Polyethylene glycol derivative 9bw induced cell death in neuroblastoma. 9bw suppressed oxidative phosphorylation in neuroblastoma cells. Mitochondrial complex I is one of the targets of 9bw.