Sulfasalazine is a synthetic salicylic acid derivative and sulfonamide which can act as an antirhematic and gastrointestinal agent. It is formulated as a prodrug, and is metabolized into active metabolites sulfapyridine and mesalazine (5-aminosalicylic acid; 5-ASA). Sulfasalazine and its metabolites have antibacterial, immunosuppressive, and anti-inflammatory properties. The compound is an inhibitor of cystine-glutamate.
|Mechanism of Action||The mechanism of Sulfasalazine is not yet elucitated but one proposed mechaanism based on in vitro and in vivo models suggests it is via the inhibition of prostalandins that results in its anti-inflammatory properties. Like methotrexate, Sulfasalazine enhances adenosine release at an inflamed site and that adenosine diminishes inflammation via occupancy of A2 receptors on inflammatory cells. It also interferes with DNA synthesis.|
|Cancer Research Applications||Certain cancers depend on uptake of cystine/cysteine. L-cysteine is the reduced form of cystine. Human prostate cancer cell lines, DU‐145 and PC‐3 were reviewed for dependence on extracellular cystine and sensitivity to Sulfasalazine, a potent inhibitor of the xc − cystine transporter. Sulfasalazine‐induced cystine/cysteine starvation leading to glutathione depletion may be useful for prostate cancer therapy (Doxsee et al, 2007). Authors found that Sulfasalazine was an inhibitor of the xc −transporter in lymphoma cells (Gout et al, 2001).|
Doxsee DW (2007) Sulfasalazine‐induced cystine starvation: Potential use for prostate cancer therapy 67(2):162-171
Gadangi P et al (1996) The anti-inflammatory mechanism of Sulfasalazine is related to adenosine release at inflamed sites. J Immunol. 156(5):1937-1941 PMID 8596047
Gout P, Buckley A, Simms C and Bruchovsky N (2001) Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the xc − cystine transporter: A new action for an old drug. Leukemia 15: 1633–1640