4-NQO induces apoptosis via p53-dependent mitochondrial signaling pathway

4-Nitroquinoline N-oxide (4-NQO) as an UV-mimetic agent leading to DNA damage is a potent mutagen and carcinogen, and can induce Apoptosis in various types of cells. However, the mechanism of Apoptosis induced by 4-NQO is still not quite clarified. In this study we found that 4-NQO could not only induce Apoptosis in KB cells, but also caused considerable damage to the mitochondrial membrane. Therefore, we inferred that 4-NQO might induce Apoptosis through the mitochondrial signaling pathway resulting from DNA damage. Further investigation showed that the Apoptosis induced by 4-NQO was p53-dependent. Furthermore, the expression levels of Bax and Bcl-2, closely related to mitochondrial signaling pathway, were up- and down-regulated, respectively. Meanwhile, the activity of caspase-9 and -3, lying in downstream of mitochondrial, was also enhanced. At the same time, the expression level of p21 also was increased by 4-NQO exposure, leading to the cell cycle arrested in G(1) phase. The results indicated that 4-NQO arrested cell cycle in G(1) phase, thus allowing enough time for DNA repair; on the Other hand, if the cellular DNA were not repaired, Apoptosis may follow through the p53-dependent mitochondrial signaling pathway, and mechanism of Apoptosis induced by 4-NQO is not exactly the same that induced by UV radiation, as the later induces Apoptosis through death receptors and mitochondrial signaling pathway.