α-Tocopheryl succinate pre-treatment attenuates quinone toxicity in prostate cancer PC3 cells.
Ilaria Bellezza, Silvia Grottelli, Leonardo Gatticchi, Anna Lisa Mierla, Alba Minelli
文献索引:Gene 539(1) , 1-7, (2014)
全文:HTML全文
摘要
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. 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. 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,quinone oxidoreductase seems to be responsible, at least in part, for the lack of the additional response. Silencing the gene and/or the inhibition ofquinone oxidoreductase activity counteracts the α-tocopheryl succinate-induced adaptive response. 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.Copyright © 2014 Elsevier B.V. All rights reserved.
相关化合物
相关文献:
2014-05-01
[Invest. Ophthalmol. Vis. Sci. 55(5) , 3012-21, (2014)]
2015-07-15
[Food Chem. 179 , 116-26, (2015)]
2015-08-01
[J. Cell Sci. 128 , 2891-902, (2015)]
2015-11-09
[Chemistry 21 , 16474-8, (2015)]
2014-06-01
[J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 960 , 52-8, (2014)]