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01-01-2018 | Laboratory Investigation

Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model

Authors: Shinya Haryu, Ryuta Saito, Wenting Jia, Takuhiro Shoji, Yui Mano, Aya Sato, Masayuki Kanamori, Yukihiko Sonoda, Oltea Sampetrean, Hideyuki Saya, Teiji Tominaga

Published in: Journal of Neuro-Oncology | Issue 1/2018

Abstract

Expression of CD44 in glioma cells was previously correlated with tumor grade and is considered a stem cell marker. CD44 stabilizes the cystine–glutamate transporter (xCT) and inhibits apoptosis in cancer stem cells (CSCs). Recently it was found that Sulfasalazine (SSZ), an anti-inflammatory drug, acts as an inhibitor of xCT and therefore has potential as a targeted therapy for CSCs. In this study, we tested an efficacy of SSZ against glioma stem cell model developed in rats. As poor penetration of blood–brain barrier resulted in insufficient efficacy of systemic SSZ treatment, SSZ was delivered locally with convection-enhanced delivery (CED). In vitro, expression of CD44 in glioma cells and efficacy of SSZ against glioma cells and glioma stem cells were confirmed. SSZ demonstrated anti-proliferative activity in a dose dependent manner against these cells. This activity was partially reversible with the addition of antioxidant, N-acetyl-l-cysteine, to the medium. In vivo, CED successfully delivered SSZ into the rat brain parenchyma. When delivered at 5 mM concentration, which was the highest possible concentration when SSZ was dissolved in water, CED of SSZ resulted in almost no tissue damage. Against highly malignant bRiTs-G3 brain tumor xenografted rat model; the glioma stem cell model, CED of SSZ at 5 mM concentration induced apoptosis and prolonged survival. Consequently, CED of SSZ induced glioma stem cell death without evidence of tissue damage to normal brain parenchyma. This strategy may be a promising targeted treatment against glioma stem cells.

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Title: Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model
Authors: Shinya Haryu
Ryuta Saito
Wenting Jia
Takuhiro Shoji
Yui Mano
Aya Sato
Masayuki Kanamori
Yukihiko Sonoda
Oltea Sampetrean
Hideyuki Saya
Teiji Tominaga
Publication date: 01-01-2018
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2621-7

At a glance: The STEP trials

Springer Medicine

Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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