Proliferative and anti-proliferative effects of thymosin α1 on cells are associated with manipulation of cellular ROS levels

Reactive oxygen species (ROS) are constantly generated and eliminated in the biological system and play important roles in a variety of physiological and pathological processes. Previous studies indicate that modulation of cellular ROS affects cell proliferation. Thymosin alpha 1 (Tα1) is a naturally occurring thymic peptide and has previously been shown to be a potential therapy for some immunodeficiencies, malignancies, and infections. However, few reports have focused on manipulation of cellular ROS level effects of Tα1. In this study, the Tα1-treated leukomonocytes, which were isolated from mice spleens, exhibited a higher ROS level and a lower reduced glutathione (GSH) level; however, HepG2 cells treated with Tα1 exhibited lower ROS level and higher GSH level. In addition, after treatment with Tα1, the population of leukomonocytes in the G2 phase increased, resulting in a slight increase in viability. However, in Tα1-treated HepG2 cells, the cell cycle was delayed in the G1 phase, thereby inhibiting tumor cell proliferation; in addition, dephosphorylation of the serine/threonine kinase Akt was detected. In conclusion, we show that Tα1 has potent anti-proliferative activity against malignant human hepatoma cells and proliferative activity against leukomonocytes associated with manipulation of oxidative stress levels which indicates the potential of Tα1 as an antitumor drug.