title: Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade.
abstract: Traditional medicinal herb Andrographis paniculata is known to possess anti-tumor activity, and its potential active compound is the diterpenoid lactone andrographolide (ANGL). In this study, we have found that ANGL inhibits tumor growth in nude mice bearing xenografted Hep3B cancer cells, concomitant with a reduction in tumor vessel counts. ANGL inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenic responses in vitro and neoangiogenesis in vivo. We also found that ANGL inhibits VEGFA-induced phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream targets such as the mitogen-activated protein kinases (MAPKs). ANGL interferes with the binding of VEGFA to VEGFR2, but has no effect on VEGFR2 kinase activity in vitro. Taken together, our results indicate that ANGL possesses anti-angiogenic activity which is mediated by preventing VEGFA-induced phosphorylation and activation of VEGFR2 and MAPKs. The present study indicates that ANGL can block tumor angiogenesis and therefore represents therapeutic potential for cancer treatment.
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Kaikai
authors.initials: K
authors.lastname: Shen
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: lichenyue1307@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xu
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Chenyuan
authors.initials: C
authors.lastname: Gong
authors.affiliation: Western Australian Institute for Medical Research, The University of Western Australia, Perth, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: ztwang@shutcm.edu.cn.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023421:Models, Animal; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004224:Diterpenes; D042461:Vascular Endothelial Growth Factor A; C030419:andrographolide; D040301:Vascular Endothelial Growth Factor Receptor-2; D020928:Mitogen-Activated Protein Kinases
keywords: Andrographolide; Mitogen-activated protein kinases; Tumor angiogenesis; Vascular endothelial growth factor A; Vascular endothelial growth factor receptor 2