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Figure 4. Antioxidants are effective cancer chemopreventatives until cancer becomes established, when they promote metastatic
progression, whereas NSAIDs as pro-oxidants are effective by overloading cancer cells with excessive ROS to eliminate metastases.
Once tumors are established, antioxidants will support and promote the further progression of cancer cells to metastasize. However, the
opposing pro-oxidants such as the NSAID celecoxib cause excessive ROS overload and induce mass cell death in metastases or sensitize
metastatic cells to enhanced chemotherapeutic killing. ROS: reactive oxygen species; HIF hypoxia-induced factor; NSAID: non-steroidal
anti-inflammatory drug; Trx: thioredoxin; TrxR: thioredoxin reductase