Oxygen is essential for aerobic organisms. On the other hand, exogenous or endogenous reactive oxygen species (ROS) can alter or even damage many cellular functions on the other hand. Oxidative stress is known to induce a wide variety of cellular responses in different cultured cell lines.

In our study, 30 minutes 0.5 mM of exogenous added hydrogen peroxide (H₂O₂) treatment was found to induce an irreversible G2/M cell cycle arrest on HONE-1. Although the mitogen-activated protein kinases (MAPKs), the c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) were activated, we demonstrated that they were not directly involved in the induction of G2/M arrest. However, blocking of the upstream kinase of ERK, the c-Raf, was able to release part of the G2/M arrest. This showed that there was a minor alternative pathway controlling the induction of cell cycle arrest, apart from the ERK pathway.

        The proceeding of G2/M phase is regulated by the cdc2-cyclin complex phosphorylation state. In our study, although the cyclin-dependent kinase inhibitor, p21 was activated, the phospho-cdc2(T161) was not being inhibited. The increase of phospho-cdc25C(S216), together with the decrease of phospho-cdc2(Y15) and phospho-cdc2(T14), and their corresponding kinases Wee1 and Myt1, indicated that the cell may have proceeded to the M phase already.

        The H₂O₂ treatment can reduce the succinate dehydrogenase (SDH) activity in mitochondria, but using the JNK and p38 inhibitors, the SDH activity can be restored. Also, the energy production of the cell was being inhibited after the H₂O₂ treatment.

        Our results indicate that H₂O₂ induced cell cycle arrest may be related to the decrease of energy production, and contribute to the ultimate fate of the cell.