In vitro and in vivo activity of the nuclear factor-kappaB inhibitor sulfasalazine in human glioblastomas.
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.
Robe
Pierre A
PA
Center for Cellular and Molecular Therapeutics, University of Liège, Liège, Belgium. Pierre.robe@ulg.ac.be
Bentires-Alj
Mohamed
M
Bonif
Marianne
M
Rogister
Bernard
B
Deprez
Manuel
M
Haddada
Heddi
H
Khac
Minh-Tuan Nguyen
MT
Jolois
Olivier
O
Erkmen
Kadir
K
Merville
Marie-Paule
MP
Black
Peter M
PM
Bours
Vincent
V
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000970:Antineoplastic Agents; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D012460:Sulfasalazine / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016328:NF-kappa B; D012460:Sulfasalazine