MMPP is a novel VEGFR2 inhibitor that suppresses angiogenesis via VEGFR2/AKT/ERK/NF-κB pathway
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Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl)phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenicprocesses, such as cell migration, invasion, tube formation, andsprouting of new vessels in human umbilical vein endothelialcells (HUVECs) and mouse aortic ring. The inhibitory mechanismof MMPP on angiogenesis involves targeting VEGFR2. MMPPshowed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stabilityand inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, andMMP9. Furthermore, conditioned medium from MMPP-treatedbreast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promiseas a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.
Abstract
Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl)phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenicprocesses, such as cell migration, invasion, tube formation, andsprouting of new vessels in human umbilical vein endothelialcells (HUVECs) and mouse aortic ring. The inhibitory mechanismof MMPP on angiogenesis involves targeting VEGFR2. MMPPshowed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stabilityand inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, andMMP9. Furthermore, conditioned medium from MMPP-treatedbreast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promiseas a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.
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