The Combination of α-Tocopheryl Succinate and Sodium Selenite on Breast Cancer: A Merit or a Demerit?

alpha-Tocopheryl succinate (alpha-TOS), a mitochondria-targeting agent, induces apoptosis in malignant cells in vitro and in vivo. Selenite is a nutritional supplement that has been shown to stimulate apoptosis in cancer cells. This study was designed to investigate the cytotoxic effect of combined treatment of alpha-TOS and sodium selenite (SSe) in vitro and in vivo and to explore their effect on apoptosis and autophagy in breast cancer. The type of interaction between alpha-TOS and SSe was evaluated and levels of oxidative stress and apoptotic and autophagic markers were determined. SSe alone showed varying degrees of cytotoxicity on all the tested cell lines. Its combination with alpha-TOS was antagonistic in vitro in MCF7 and in vivo in mice bearing Ehrlich tumor compared to alpha-TOS-treated one. Combination of TOS with 2 mu M of SSe increased the level of glutathione without changes in antiapoptotic markers Bcl-2 and Mcl-1 at 16 and 48 hrs. SSe decreased caspase 3 activity and protein level of caspases 7 and 9, while it increased autophagic markers beclin-1 and LC3B protein levels of MCF7 cells treated with alpha-TOS. In conclusion, SSe antagonizes alpha-TOS-induced apoptosis via inhibition of oxidative stress and promoting prosurvival machinery of autophagy.