Resveratrol plus low-dose hydroxyurea compared to high-dose hydroxyurea alone is more effective in -globin gene expression and ROS reduction in K562 cells

Hydroxyurea (HU) is an anti-cancer drug that is used for the treatment of hemoglobinopathies as a gamma-globin inducer. However, its dose-dependent effects have hampered its clinical reliability. Resveratrol (RSV) is an antioxidant and gamma-globin inducer. The present study aimed to assess their combined effects on the gamma-globin gene expression and reactive oxygen species (ROS) level of K562 cells. The results indicated that the gamma-globin gene expression was approximately two folds higher in the group treated with RSV 50 mu M + HU 25 mu M in comparison to HU 100 mu M alone (***p < 0.001). However, there was an inverse relationship between the expression of gamma-globin gene and HU concentration in the combined groups. Furthermore, the combinations of RSV and HU significantly reduced ROS levels compared to single drugs. Overall, the combination of these compounds was an appropriate strategy for increasing gamma-globin expression, reducing oxidant levels, and alleviating the adverse effects of HU. [GRAPHICS] .