Epigallocatechin-3-gallate Antagonizes The Cytotoxicity Of Sodium Selenite And Its Mechanisms

Polyphenols such as(-)-epigalocatechin gallate(EGCG)are widely consumed in daily diets and have potent antioxidant capacity.Selenium is one of the necessary trace elements for humans and has anti-cancer properties.A large number of epidemiological and clinical studies have shown that selenium can effectively inhibit the occurrence of a variety of cancers,but the SELECT trail has reached the opposite conclusion.Many possible reasons inducing failure have been proposed,but it is still inconclusive.In order to further explore the potential causes of selenium cancer suppression failure,the interaction between sodium selenite and polyphenols was studied in vivo and in vitro.In chemical system,sodium selenite can be metabolized through glutathione(GSH)system,glutaredoxin(Grx)coupled GSH system and thioredoxin(Trx)system to generate a large amount of ROS,which were markedly inhibited by EGCG in a dosedependent manner.In cell experiments,EGCG significantly inhibited the cytotoxicity of sodium selenite to TCA cancer cells,suggesting that the ability of proliferation and growth,and invasion and metastasis of cancer cells was enhanced.Moreover,on the basis of making no difference of key enzymes activity in GSH and Trx systems,EGCG antagonizes the cytotoxicity of sodium selenite by decreasing the drug sensitivity of sodium selenite to cancer cells,inhibiting DNA damage,and promoting the expression of apoptosis inhibitory proteins,characterized by the increase of phosphorylated histone 2A variant X(y-H2A.X),the decreased levels of ROS,cyclooxygenase 2(COX-2),X-linked inhibitor of apoptosis protein(XIAP),survivin,B-cell lymphoma 2(Bcl-2),caspase 3 and caspase 8.In the animal model of hepatocellular carcinoma H22 ascites,EGCG can reduce the killing effect of sodium selenite on H22 cells by inhibiting ROS level.In chemical and cell experiments,we also found that quercetin,chlorogenic acid,resveratrol and other polyphenols combined with sodium selenite still showed antagonistic effects.Taken together,this study found that polyphenols such as EGCG can antagonize the cytotoxicity of sodium selenite by inhibiting ROS level,suggesting that polyphenols may reduce the anti-cancer effect of selenium.Therefore,when sodium selenite is used as an anticancer drug,it should be paid to the intake of polyphenols.