7-Difluoromethyl-5,4'-dimethoxygenistein exerts anti-angiogenic effects on acute promyelocytic leukemia HL-60 cells by inhibiting the TLR4/NF-κB signaling pathway

Abstract

Angiogenesis plays an important role in the development and metastasis of tumors, and anti-angiogenesis agents are used to treat tumors. For example, the acute promyelocytic leukemia (aPl) may be treated with arsenic trioxide. angiogenesis in aPl is a multi-step dynamic equilibrium process coordinated by various angiogenic stimulators and inhibitors, which play key roles in the occurrence, progression and chemosensitivity of this disease. our research group previously synthesized 7-difluoromethyl-5,4'-dimethoxygen-istein (dFMG), and found that it inhibits angiogenesis during atherosclerotic plaque formation. in the present study, the effect and mechanism of dFMG in angiogenesis induced by aPl Hl-60 cells was investigated using a chick embryo chorioallantoic membrane model and Matrigel tubule formation assays. The results obtained revealed an anti-angiogenesis effect of dFMG towards Hl-60 cells. When the Toll-like receptor 4/nuclear factor-κB (TLR4/nF-κB) signaling pathway was inhibited, the anti-angiogenic effect of dFMG was further enhanced. However, when the TLR4/nF-κB signaling pathway was activated, the anti-angiogenic effect of dFMG was attenuated. These results demonstrated that dFMG inhibits angiogenesis induced by aPl Hl-60 cells, and provides insights into the mechanism by which dFMG inhibits the TLR4/nF-κB signaling pathway. in conclusion, in the present study, the anti-angiogenesis effect of dFMG on aPl has been reported, and the mechanism by which dFMG induced the anti-angiogenesis effect was explored. These findings have provided a potential new drug candidate for the treatment of patients with aPl.