Tolfenamic acid

• tolfenamic acid An orally available, benzoic acid derivative and a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic, analgesic and potential anti-neoplastic activities. Tolfenamic acid inhibits the activity of the enzymes cyclooxygenase (COX) I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. The decrease in prostaglandin synthesis results in the therapeutic effects of this agent. Tolfenamic acid also inhibits thromboxane A2 synthesis, by thromboxane synthase, which decreases platelet aggregation. In addition, this agent exerts anti-tumor effects through COX-dependent and independent pathways. Specifically, this agent induces the production of reactive oxygen species, causes DNA damage, increases nuclear factor-kappa B (NF-kB) activation and the expression of activating transcription factor 3 (ATF3) and NSAID-activated gene-1 (NAG1), and inhibits the expression of specificity proteins (Sp), which reduces the expression of Sp-dependent anti-apoptotic and growth-promoting proteins. Altogether, this enhances tumor cell apoptosis, and reduces tumor cell growth and angiogenesis.

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