Positive Health Online

Abstract

BELLEZZA and COLLEAGUES, (1)Dipartimento di Medicina Sperimentale, Piazzale Gambuli, S. Andrea delle Fratte, 06132 Perugia, Italy (2)Dipartimento di Medicina Sperimentale, Piazzale Gambuli, S. Andrea delle Fratte, 06132 Perugia, Italy. Electronic address: alba.minelli@unipg.it  studied the effects of α-Tocopheryl succinate pre-treatment in prostate cancer PC3 cells

Background

α-Tocopheryl succinate is one of the most effective analogues of vitamin E for inhibiting cell proliferation and inducing cell death in a variety of cancerous cell lines while sparing normal cells or tissues. αTocopheryl succinate inhibits oxidative phosphorylation at the level of mitochondrial complexes I and II, thus enhancing reactive oxygen species generation which, in turn, induces the expression of Nrf2-driven antioxidant/detoxifying genes.

Methodology

The cytoprotective role of Nrf2 downstream genes/proteins prompted us to investigate whether and how α-tocopheryl succinate increases resistance of PC3 prostate cancer cells to pro-oxidant damage. A 4h α-tocopheryl succinate pre-treatment increases glutathione intracellular content, indicating that the vitamin E derivative is capable of training the cells to react to an oxidative insult.

Results

We found that α-tocopheryl succinate pre-treatment does not enhance paraquat-/hydroquinone-induced cytotoxicity whereas it exhibits an additional/synergistic effect on H₂O₂₋/docetaxel-induced cytotoxicity. While glutathione and heme oxygenase-1 are not involved in α-tocopheryl succinate-induced adaptive response to paraquat,NAD(P)H: quinone oxidoreductase seems to be responsible, at least in part, for the lack of the additional response. Silencing the gene and/or the inhibition of NAD(P)H: quinone oxidoreductase activity counteracts the α-tocopheryl succinate-induced adaptive response.

Conclusion

In conclusion, the adaptive response to α-tocopheryl succinate shows that the activation of Nrf2 can promote the survival of cancer cells in an unfavourable environment.

References

Bellezza I(1), Grottelli S(1), Gatticchi L(1), Mierla AL(1) and Minelli A(2). α-Tocopheryl succinate pre-treatment attenuates quinone toxicity in prostate cancer PC3 cells. ; Gene 539(1):1-7. doi: 10.1016/j.gene.2014.02.009. Apr 10 2014 Epub 2014 Feb 12.