Sulfasalazine (Azulfidine) is a synthetic salicylic acid derivative with affinity for connective tissues containing elastin and formulated as a prodrug

Sulfasalazine, like methotrexate, enhances adenosine release at an inflamed site and that adenosine diminishes inflammation via occupancy of A2 receptors on inflammatory cells. [1] Sulfasalazine treatment for 4 hours inhibits kappaB-dependent transcription with an IC50 value of approximately 0.625 mM. Sulfasalazine (2.5 mM) results in cell death of T-lymphocytes in a dose- and time-dependent manner. Sulfasalazine but not 5ASA or sulfapyridine, strongly inhibits NF-kappaB activation and potently induces apoptosis in T-lymphocytes. [2] Sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid (5-ASA; mesalamine) by colonic bacteria, and the latter, too, is reported to suppress NF-kappaB activity. Sulfasalazine but not its cleaved form 5-ASA causes a dose-dependent inhibition of glioma growth, this effect is entirely attributable to the inhibition of cystine uptake via the system x(c)(-) cystine-glutamate transporter. Sulfasalazine inhibits cystine uptake causing a chronic depletion of intracellular GSH and consequently compromised cellular redox defense which stymied tumor growth. [3]

Sulfasalazine markedly decreases the number of leukocytes that accumulated in the inflamed (carrageenan, 2 mg/ml) air pouch in the murine air pouch model of inflammation. Sulfasalazine treatment promotes a marked increase in splenocyte 5-aminoimidazole-4-carboxamidoribonucleotide (AICAR) concentration, which is consistent with the in vitro observation that sulfasalazine inhibits AICAR transformylase. [1]

Sulfasalazine is dissolved in culture medium. SW620 cells are grown in Dulbecco's modified Eagle medium, supplemented with 10% heat-inactivated FCS, 2 mmol/liter glutamine, and 1% (wt/vol) penicillin/streptomycin. SW620 cells are transfected with the 3xIgkBLuc reporter construct. After 18 h, cells are incubated with either medium alone or with sulfasalazine (0.1, 0.2, 0.5, 1, 2, 5 mM) before stimulation with TNFα, LPS, or PMA. Luciferase assay is performed[1].