title: The Combination of α-Tocopheryl Succinate and Sodium Selenite on Breast Cancer: A Merit or a Demerit?
abstract: α-Tocopheryl succinate (α-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 α-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 α-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 α-TOS was antagonistic in vitro in MCF7 and in vivo in mice bearing Ehrlich tumor compared to α-TOS-treated one. Combination of TOS with 2 μM 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 α-TOS. In conclusion, SSe antagonizes α-TOS-induced apoptosis via inhibition of oxidative stress and promoting prosurvival machinery of autophagy.
authors.affiliation: Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Doaa M
authors.initials: DM
authors.lastname: Badr
authors.affiliation: Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Hafez F
authors.initials: HF
authors.lastname: Hafez
authors.affiliation: Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo 11796, Egypt.
authors.forename: Azza M
authors.initials: AM
authors.lastname: Agha
authors.affiliation: Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Shouman
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D020169:Caspases; D024502:alpha-Tocopherol; D018038:Sodium Selenite