Coenzyme Q2 induced p53-dependent apoptosis.
Coenzyme Q functions as an electron carrier and reversibly changes to either an oxidized (CoQ), intermediate (CoQ.-), or reduced (CoQH2) form within a biomembrane. The CoQH2 form also acts as an antioxidant and prevents cell death, and thus has been successfully used as a supplement. On the other hand, the value of the CoQ/CoQH2 ratio has been shown to increase in a number of diseases, presumably due to an anti-proliferative effect involving CoQ. In the present study, we examined the effect of CoQ and its isoprenoid side chain length variants on the growth of cells having different p53 statuses. Treatment with CoQs having shorter isoprenoid chains, especially CoQ2, induced apoptosis in p53-point mutated BALL-1 cells, whereas treatment with longer isoprenoid chains did not. However, CoQ2 did not induce apoptosis in either a p53 wild-type cell line or a p53 null mutant cell line. These results indicated that the induction of apoptosis by CoQ2 was dependent on p53 protein levels. Moreover, CoQ2 induced reactive oxygen species (ROS) and the phosphorylation of p53. An antioxidant, l-ascorbic acid, inhibited CoQ2-induced p53 phosphorylation and further apoptotic stimuli. Overall, these results suggested that short tail CoQ induces ROS generation and further p53-dependent apoptosis.
Esaka
Yuki
Y
Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Nagahara
Yukitoshi
Y
Hasome
Yoshimune
Y
Nishio
Reiji
R
Ikekita
Masahiko
M
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism* / Q000494:pharmacology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D014451:Ubiquinone; C025204:Ubiquinone Q2; D001205:Ascorbic Acid