Acta Pharmacologica Sinica 2008 December; 29 (12): 1451-1458; doi: 10.1111/j.1745-7254.2008.00902.x

Aim: To determine whether the antitumor factor nm23 is related with antioxidation.

Methods: Full-length human nm23-H1 was cloned into a mammalian-expressing vector and transiently introduced into HeLa cells.

Results: A remarkably low level of reactive oxygen species (ROS) was detected in the cells over-expressing nm23-H1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays found that the cells transfected with a nm23-H1-expressing plasmid had higher viability and stronger resistance to oxidative stress. Immunoprecipitation tests revealed that endogenous nm23-H1 formed a protein complex with p53. Furthermore, the intracellular levels of p53 and p53-regulated gene GPX1 were obviously increased in the cells overexpressing nm23-H1. The downregulation of p53 in the cells overexpressing nm23-H1 resulted in a higher cellular ROS level and lower cell viability.

Conclusion: The findings suggest that nm23-H1 may act as a cellular protector against oxidative stress, possibly triggering the p53-related antioxidative pathway.

Keywords: nm23-H1; oxidative stress; reactive oxygen species; cell viability; p53; GPX1