Non-antioxidant properties of α-tocopherol reduce the anticancer activity of several protein Kinase inhibitors in vitro
PLoS ONE. 2012-05-08; 7(5): e36811
DOI: 10.1371/journal.pone.0036811
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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.