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

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

研究成果: Article

5 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)23-31
ページ数9
ジャーナルJournal of Neuro-Oncology
136
発行部数1
DOI
出版物ステータスPublished - 2018 1 1

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

フィンガープリント Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Haryu, S., Saito, R., Jia, W., Shoji, T., Mano, Y., Sato, A., Kanamori, M., Sonoda, Y., Sampetrean, O., Saya, H., & Tominaga, T. (2018). Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model. Journal of Neuro-Oncology, 136(1), 23-31. https://doi.org/10.1007/s11060-017-2621-7