Induction of urokinase-type plasminogen activator by sodium salicylate in a glioblastoma cell strain

Urokinase-type plasminogen activator (uPA) is an extracellular protease involved in many physiological and pathological processes. In this paper its induction by sodium salicylate (NaSal) in A1235 glioblastoma cell strain is described. Maximum uPA induction was observed 24-36 h after NaSal treatment and levels of enzyme produced were 5-7 times as high as those of untreated control. uPA induction was based on the uPA promoter activation - both, 2.2kb and 5.5kb uPA promoters, containing single and two AP-1/PEA3 binding sites, respectively, were activated. NaSal also caused substantial cell growth inhibition and cell morphology changes. Curcumin and pyrrolidine dithiocarbamate (PDTC), NF-kappaB inhibitors, did not abrogate NaSal-induced uPA promoter activity, nor induced uPA, suggesting that NF-kappaB is not involved in this uPA induction. This observation was also confirmed by immunoblot analysis on I kappaB. Aspirin (acetylsalicylate) also activated uPA promoter and induced uPA production. The results in this paper suggest that NaSal induced uPA production is based on the uPA promoter activation through an NF-kappaB independent pathway.