Dual functionality of the antimicrobial agent taurolidine which demonstrates effective anti-tumor properties in pediatric neuroblastoma Journal Article

Authors: Swift, L.; Zhang, C.; Kovalchuk, O.; Boklan, J.; Trippett, T.; Narendran, A.
Article Title: Dual functionality of the antimicrobial agent taurolidine which demonstrates effective anti-tumor properties in pediatric neuroblastoma
Abstract: High-risk, relapsed and refractory neuroblastoma are associated with poor 5-years survival rates, demonstrating the need for investigational therapeutic agents to treat this disease. Taurolidine is derived from the aminosulfoacid taurine and has known anti-microbial and anti-inflammatory properties. Taurolidine has also demonstrated anti-neoplastic effects in a range of cancers, providing the rationale to investigate the activity of taurolidine against neuroblastoma in preclinical studies. We investigated the in vitro activity of taurolidine against neuroblastoma using the alamar blue cytotoxicity assay, phase-contrast light microscopy, western blotting and analysis of global gene expression by RNA-Seq. In vivo activity of taurolidine was evaluated using mouse xenograft models. In vitro pre-clinical data show that taurolidine is cytotoxic to neuroblastoma cell lines, inducing cell death by apoptosis. Analysis of global gene expression and determination of signaling pathway activation scores using the in silico Pathway Activation Network Decomposition Analysis (iPANDA) platform indicates that taurolidine has an effect on the Notch, mitogen-activated protein kinase (MAPK) and interleukin-10 (IL-10) signaling pathways. In vivo experiments in xenograft mouse models show that taurolidine decreases tumor growth and improves survival. These results provide supportive pre-clinical data on the activity of taurolidine against neuroblastoma. The findings support the rationale for further evaluation of taurolidine for the treatment of relapsed/refractory neuroblastoma patients in an early phase clinical trial. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: signal transduction; survival; mitogen activated protein kinase; child; controlled study; human cell; microscopy; nonhuman; mouse; cell viability; apoptosis; gene expression; interleukin 10; animal experiment; animal model; notch receptor; in vivo study; antineoplastic activity; in vitro study; tumor xenograft; cancer inhibition; neuroblastoma; western blotting; drug cytotoxicity; pediatric oncology; novel therapeutics; notch signaling; mapk signaling; human; female; priority journal; article; rna sequencing; taurolidine; anti-microbial; il 10 signaling pathway; phase contrast light microscopy; resazurin assay
Journal Title: Investigational New Drugs
Volume: 38
Issue: 3
ISSN: 0167-6997
Publisher: Springer  
Date Published: 2020-06-01
Start Page: 690
End Page: 699
Language: English
DOI: 10.1007/s10637-019-00816-1
PUBMED: 31264069
PROVIDER: scopus
Notes: Article -- Export Date: 1 June 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Tanya M Trippett
    110 Trippett