title: Tryptanthrin inhibits angiogenesis by targeting the VEGFR2-mediated ERK1/2 signalling pathway.
abstract: Angiogenesis is a key step for tumour growth and metastasis, and anti-angiogenesis has been proposed as an important strategy for cancer therapy. Tryptanthrin is a weakly basic alkaloid isolated from the dried roots of medicinal indigo plants and has been shown to possess anti-tumour activities on various cancer cell types. This study aims to investigate the in vitro and in vivo anti-angiogenic activities of tryptanthrin and to unravel its underlying molecular action mechanisms. Our results show that tryptanthrin inhibited the in vitro proliferation, migration, and tube formation of the human microvascular endothelial cells (HMEC-1) in a concentration-dependent manner and significantly suppressed angiogenesis in Matrigel plugs in mice. Mechanistic studies indicated that tryptanthrin reduced the expression of several pro-angiogenic factors (Ang-1, PDGFB and MMP2). Tryptanthrin was also found to suppress the VEGFR2-mediated ERK1/2 signalling pathway in HMEC-1 cells and molecular docking simulation indicated that tryptanthrin could bound to the ATP-binding site of VEGFR2. Collectively, the present study demonstrated that tryptanthrin exhibited both in vitro and in vivo anti-angiogenic activities by targeting the VEGFR2-mediated ERK1/2 signalling pathway and might have therapeutic potential for the treatment of angiogenesis-related diseases.
authors.affiliation: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, HKSAR, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Liao
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, HKSAR, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon Tong, HKSAR, China.
authors.forename: Nai-ki
authors.initials: NK
authors.lastname: Mak
authors.affiliation: Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, HKSAR, China.
authors.forename: Kwok-nam
authors.initials: KN
authors.lastname: Leung
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D011799:Quinazolines; C046243:tryptanthrine; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2