Natural forms of vitamin E inhibited leukotriene B4 generation and 5‐lipoxygenase translocation in Ca2+ ionophore‐activated human HL‐60 cells

Abstract

Leukotriene B4 (LTB4) generated by 5‐lipoxygenase (5‐LOX)‐catalyzed reaction plays an important role in regulation of inflammation and contributes to the development of cancer. Vitamin E has eight natural forms, i.e., alpha‐, beta‐, gamma‐ and delta‐tocopherol and four corresponding tocotrienols. Previous studies of the effect of alpha‐tocopherol on 5‐LOX‐catalyzed reaction revealed inconsistent results. In the present study, we examined the effect of various forms of vitamin E on leukotriene B4 generation in neutrophil‐like cells that were differentiated from HL‐60 cells by 1.25% DMSO for 5–6 days. Activation of HL‐60 cells by calcium ionophore A23187 led to a markedly increase of LTB4. Gamma‐tocotrienol, delta‐tocophoerol and gamma‐tocopherol dose‐dependently inhibited LTB4 with apparent IC50s at 25–50uM. In contrast, alpha‐tocopherol did not show any significant inhibition at concentrations of 10–50uM. Gamma‐ and delta‐tocopherol significantly inhibited A23187‐induced 5‐LOX translocation from cytoplasm to nuclear compartment, a critical step for leukotriene formation. These observations support the notion that certain vitamin E forms may have anti‐inflammatory activity which leads to disease prevention and therapy. Studies are currently undertaken to further investigate the mechanism underlying observed effects. (supported by NIH R01AT001821)