| RRC ID |
52390
|
| Author |
Haryu S, Saito R, Jia W, Shoji T, Mano Y, Sato A, Kanamori M, Sonoda Y, Sampetrean O, Saya H, Tominaga T.
|
| Title |
Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model.
|
| Journal |
J Neurooncol
|
| 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.
|
| Volume |
136(1)
|
| Pages |
23-31
|
| Published |
2018-1-1
|
| DOI |
10.1007/s11060-017-2621-7
|
| PII |
10.1007/s11060-017-2621-7
|
| PMID |
28929335
|
| MeSH |
Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Antineoplastic Agents / administration & dosage*
Apoptosis / drug effects
Brain Chemistry
Brain Neoplasms / drug therapy*
Brain Neoplasms / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Convection
Disease Models, Animal
Drug Delivery Systems
Glioma / drug therapy*
Glioma / metabolism
Humans
Hyaluronan Receptors / metabolism
Male
Mice
Neoplastic Stem Cells / drug effects
Rats
Sulfasalazine / administration & dosage*
Survival Analysis
Xenograft Model Antitumor Assays
|
| IF |
3.06
|
| Times Cited |
4
|
| Resource |
| Human and Animal Cells |
A172(RCB2530) |
