In vitro and In vivo Activity of the Nuclear Factor-κB Inhibitor Sulfasalazine in Human Glioblastomas

• Published in: Clinical cancer research Vol. 10; no. 16; pp. 5595 - 5603
• Main Authors: ROBE, Pierre A, BENTIRES-ALJ, Mohamed, BLACK, Peter M, BOURS, Vincent, BONIF, Marianne, ROGISTER, Bernard, DEPREZ, Manuel, HADDADA, Heddi, NGUYEN KHAC, Minh-Tuan, JOLOIS, Olivier, ERKMEN, Kadir, MERVILLE, Marie-Paule
• Format: Journal Article Web Resource
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.2004; American Association for Cancer Research, Inc. (AACR)
• Subjects: Anti-Inflammatory Agents, Non-Steroidal/toxicity; Antineoplastic Agents; Biological and medical sciences; Brain Neoplasms/drug therapy/pathology; Cell Line, Tumor; Gene Therapy; Glioblastoma/drug therapy/pathology; Human health sciences; Humans; Medical sciences; Neurologie; Neurology; NF-kappa B/antagonists & inhibitors; Pharmacology. Drug treatments; Sciences de la santé humaine; Sulfasalazine/toxicity; Tumor Cells, Cultured; Tumors; Sulfanilamide derivatives; Human; Nervous system diseases; Sulfonamide; Glioblastoma; Activity; Malignant tumor; In vitro; Malignant glioma; In vivo; Central nervous system disease; Sulfasalazine; Inhibitor; Transcription factor NFκB
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0392

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)-κB 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-κB, 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-κB. 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.