title: Contrasting effects of α-tocopheryl succinate on cisplatin- and etoposide-induced apoptosis.
abstract: Targeting mitochondria is a promising strategy in tumor cell elimination. d-α-tocopheryl succinate (α-TOS), a redox-silent analog of vitamin E, is a potentially powerful tool for fighting tumors by directly affecting mitochondria. However, when used at low concentrations it can suppress apoptosis induced by the conventionally used anticancer drug cisplatin. In cells treated with cisplatin, 30μM α-TOS prominently attenuated the manifestation of characteristic features of apoptosis - release of cytochrome c from mitochondria, caspase-3-like activity, and cleavage of poly(ADP-ribose) polymerase. In contrast, cell death induced by etoposide was not inhibited but rather stimulated by α-TOS. Thus, co-treatment with α-TOS and conventional antitumor drugs should be carried out with caution.
authors.affiliation: Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, Stockholm, SE-171 77 Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Kruspig
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gogvadze
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis; D002460:Cell Line; D002945:Cisplatin / Q000378:metabolism*; D004347:Drug Interactions; D005047:Etoposide / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D024502:alpha-Tocopherol / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D024502:alpha-Tocopherol; D002945:Cisplatin