Anti-angiogenic effects of lycopene through immunomodualtion of cytokine secretion in human peripheral blood mononuclear cells ★

The carotenoid lycopene has been reported to possess anti-metastatic activity which may be associated with immunomodulation. However, the anti-angiogenic effects and mechanisms of action of lycopene have not been reported. In this study, we investigated the immunomodulatory effect on in vitro and ex vivo angiogenesis of lycopene. We found that the proliferation, migration and the matrigel tube formation of human umbilical vein endothelial cells (HUVECs) was remarkably inhibited by conditioned medium (CM) of human peripheral blood mononuclear cells (MNC-CM) stimulated with various dose (1-10 μmol/L) of lycopene (LP-MNC-CM). LP-MNC-CM treatment inhibited ex vivo angiogenesis, as revealed by chicken egg chorioallantoic membrane assay. We further examined the effects of lycopene stimulation on cytokine levels in MNC and showed that, as compared to the control, lycopene (10 μmol/L) significantly (P<.001) up-regulated interleukin (IL)-12 by 163% and interferon (IFN)-γ by 531%. Furthermore, pre-treatment of HUVECs with dexamethasone, an IL-12 inhibitor, blocked the anti-angiogenic effects of LP-MNC-CM in parallel with inhibition of IL-12 and IFN-γ induction in MNC. These results demonstrate that lycopene has a potent anti-angiogenic effect and that these effect may be associated with its up-regulation of IL-12 and IFN-γ.