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MMPP is a novel VEGFR2 inhibitor that suppresses angiogenesis via VEGFR2/AKT/ERK/NF-リB pathway
Na-Yeon Kim 1 (Graduate student), Hyo-Min Park 1 (Graduate student), Jae-Young Park 1 (Graduate student), Uijin Kim2 (Graduate student), Ha Youn Shin 2 (Professor), Hee Pom Lee3 (Professor), Jin Tae Hong 3 (Professor), Do-Young Yoon 1,* (Professor)
1Department of Bioscience and Biotechnology and 2Department of Biomedical Science and Engineering, Konkuk University,
3College of Pharmacy & Medical Research Center, Chungbuk National University
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 angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-リB, and it downregulated NF-リB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/ NF-リB signaling pathway.
Abstract, Accepted Manuscript(in press) [Submitted on August 16, 2023, Accepted on November 3, 2023]
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