alpha-Tocopheryl succinate pre-treatment attenuates quinone toxicity in prostate cancer PC3 cells

作者：Bellezza Ilaria; Grottelli Silvia; Gatticchi Leonardo; Mierla Anna Lisa; Minelli Alba^*

来源：Gene, 2014, 539(1): 1-7.

DOI：10.1016/j.gene.2014.02.009

• Adaptive response
• Detoxification
• Nrf2
• NQO1

alpha-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. alpha Tocopheryl 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 a-tocopheryl succinate increases resistance of PC3 prostate cancer cells to pro-oxidant damage. A 4 h alpha-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 alpha-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 alpha-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 a-tocopheryl succinate-induced adaptive response. In conclusion, t

• 出版日期2014-4-10
• 单位Perugia