TY - JOUR
T1 - In vitro and in vivo activity of the nuclear factor-kappaB inhibitor sulfasalazine in human glioblastomas
AU - Robe, Pierre A
AU - Bentires-Alj, Mohamed
AU - Bonif, Marianne
AU - Rogister, Bernard
AU - Deprez, Manuel
AU - Haddada, Heddi
AU - Khac, Minh-Tuan Nguyen
AU - Jolois, Olivier
AU - Erkmen, Kadir
AU - Merville, Marie-Paule
AU - Black, Peter M
AU - Bours, Vincent
PY - 2004/8/15
Y1 - 2004/8/15
N2 - Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment.
AB - Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment.
KW - Anti-Inflammatory Agents, Non-Steroidal/toxicity
KW - Antineoplastic Agents
KW - Brain Neoplasms/drug therapy
KW - Cell Line, Tumor
KW - Genetic Therapy
KW - Glioblastoma/drug therapy
KW - Humans
KW - NF-kappa B/antagonists & inhibitors
KW - Sulfasalazine/toxicity
KW - Tumor Cells, Cultured
U2 - 10.1158/1078-0432.CCR-03-0392
DO - 10.1158/1078-0432.CCR-03-0392
M3 - Article
C2 - 15328202
SN - 1078-0432
VL - 10
SP - 5595
EP - 5603
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -