High cytotoxicity of alpha-tocopheryl hemisuccinate to cancer cells is due to failure of their antioxidative defense systems.
Alpha-tocopheryl hemisuccinate (TS) has been reported to induce apoptosis in various cells, and to show higher toxicity to cancer cells than to normal cells. In this study, although TS induced apoptosis in both a mouse breast normal cell line NMuMG and a mouse breast cancer cell line C127I, the latter were more susceptible to TS. TS-induced apoptosis in C127I was inhibited by superoxide dismutase, alpha-tocopherol and butylated hydroxyanisol. From these results, superoxide (O(2)(-)) itself and reactive oxygen species derived from O(2)(-) and/or free radicals are assumed to be associated with TS toxicity, and the high toxicity of TS to cancer cells is suggested to be due to failure of their antioxidative defense systems.
Kogure
Kentaro
K
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1-78, Tokushima 770-8505, Japan.
Hama
Susumu
S
Manabe
Sachie
S
Tokumura
Akira
A
Fukuzawa
Kenji
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002083:Butylated Hydroxyanisole; D002273:Carcinogens; D002460:Cell Line; D002470:Cell Survival; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D024505:Tocopherols; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity*; D024502:alpha-Tocopherol / Q000494:pharmacology
D000975:Antioxidants; D002273:Carcinogens; D005609:Free Radicals; D013481:Superoxides; D014810:Vitamin E; D002083:Butylated Hydroxyanisole; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol; D024505:Tocopherols