title: Non-antioxidant properties of α-tocopherol reduce the anticancer activity of several protein kinase inhibitors in vitro.
abstract: The antioxidant properties of α-tocopherol have been proposed to play a beneficial chemopreventive role against cancer. However, emerging data also indicate that it may exert contrasting effects on the efficacy of chemotherapeutic treatments when given as dietary supplement, being in that case harmful for patients. This dual role of α-tocopherol and, in particular, its effects on the efficacy of anticancer drugs remains poorly documented. For this purpose, we studied here, using high throughput flow cytometry, the direct impact of α-tocopherol on apoptosis and cell cycle arrest induced by different cytotoxic agents on various models of cancer cell lines in vitro. Our results indicate that physiologically relevant concentrations of α-tocopherol strongly compromise the cytotoxic and cytostatic action of various protein kinase inhibitors (KI), while other classes of chemotherapeutic agents or apoptosis inducers are unaffected by this vitamin. Interestingly, these anti-chemotherapeutic effects of α-tocopherol appear to be unrelated to its antioxidant properties since a variety of other antioxidants were completely neutral toward KI-induced cell cycle arrest and cell death. In conclusion, our data suggest that dietary α-tocopherol could limit KI effects on tumour cells, and, by extent, that this could result in a reduction of the clinical efficacy of anti-cancer treatments based on KI molecules.
authors.affiliation: INSERM U916, VINCO, Institut Bergonié, Université Victor Segalen Bordeaux 2, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pédeboscq
authors.forename: Christophe
authors.initials: C
authors.lastname: Rey
authors.forename: Muriel
authors.initials: M
authors.lastname: Petit
authors.forename: Catherine
authors.initials: C
authors.lastname: Harpey
authors.forename: Francesca
authors.initials: F
authors.lastname: De Giorgi
authors.forename: François
authors.initials: F
authors.lastname: Ichas
authors.forename: Lydia
authors.initials: L
authors.lastname: Lartigue
mesh_terms: D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D019587:Dietary Supplements / Q000009:adverse effects; D004336:Drug Antagonism; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014815:Vitamins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D014815:Vitamins; D024502:alpha-Tocopherol