Intracellular reduction of coenzyme Q homologues with a short isoprenoid side chain induces apoptosis of HeLa cells.

Coenzyme Q (CoQ) is an essential factor of the mitochondrial respiratory chain. CoQ homologues with different lengths of the isoprenoid side chain are widely distributed in nature, but little is known about the relationship between the isoprenoid side chain length and biological function; therefore, we examined the effects of CoQ homologues on HeLa cells. When CoQ homologues with a shorter isoprenoid side chain than CoQ4 were added to HeLa cells, they induced cell death, and the order of cytotoxic intensity was as follows: CoQ0 ≫ CoQ3 ≈ CoQ1 > CoQ2 ≫ CoQ4. Furthermore, we found that CoQ1, CoQ2 and CoQ3 could induce caspase-mediated apoptosis, and the order of intensity was as follows: CoQ3 > CoQ2 ≥ CoQ1. We could not identify the participation of reactive oxygen species in the apoptosis induction, but observed that an NAD(P)H dehydrogenase (quinone) 1 (NQO1) inhibitor, dicumarol, could inhibit not only the intracellular reduction of the homologues but also apoptosis. However, because dicumarol did not affect well-known apoptosis inducers, such as anti-Fas IgG, tumor necrosis factor (TNF)-α, TNF-related apoptosis-inducing ligand, UV-B and H2O2 of HeLa cells at all, we concluded that NQO1-related intracellular reduction of CoQ, or its reduced product, ubiquinol, may participate in the apoptosis induction of HeLa cells.