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 (CoQH(2)) form within a biomembrane. The CoQH(2) 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/CoQH(2) 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 CoQ(2), induced apoptosis in p53-point mutated BALL-1 cells, whereas treatment with longer isoprenoid chains did not. However, CoQ(2) 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 CoQ(2) was dependent on p53 protein levels. Moreover, CoQ(2) induced reactive oxygen species (ROS) and the phosphorylation of p53., An antioxidant, L-ascorbic acid, inhibited CoQ(2)-induced p53 phosphorylation and further apoptotic stimuli. Overall, these results suggested that short tail CoQ induces ROS generation and further p53-dependent apoptosis. (c) 2005 Elsevier B.V. All rights reserved.