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

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′-dimethoxygenistein (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.