title: Anti-angiogenic activity of a new andrographolide derivative in zebrafish and HUVECs.
abstract: Andrographolide is among the most promising anti-tumor and anti-angiogenic components in Andrographis paniculata but its poor bioavailability and limited efficacy pose difficulties for its therapeutic development. Therefore, improving its pharmaceutical features and potency, by modifying its chemical structure, is desirable. In the present study, a new andrographolide derivative (AGP-40) was synthesized and characterized for its anti-angiogenic properties. Human umbilical vein endothelial cells (HUVECs) and zebrafish models were used to identify the anti-angiogenic activity of AGP-40. AGP-40 significantly suppressed the formation of blood vessels in zebrafish and inhibited proliferation, migration and tube formation in vitro. The anti-angiogenic effects of AGP-40 are at least partially mediated via the PI3K/Akt and MEK/Erk(1/2) signaling pathways. Furthermore, AGP-40 exhibited stronger anti-proliferative effects than andrographolide against A549, HepG2, Hela cancer cell lines. This study is the first to demonstrate the promising anti-angiogenic activity of the new andrographolide derivative AGP-40. Our results indicate that AGP-40 could serve as a potential therapeutic agent for the treatment and prevention of diseases associated with excessive angiogenesis.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
authors.forename: Yuran
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address: judychanyw@hotmail.com.
authors.forename: Judy Yuet-Wa
authors.initials: JY
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Cui
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
authors.forename: Decai
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China. Electronic address: gczhou@njtech.edu.cn.
authors.forename: Guo-Chun
authors.initials: GC
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D004224:Diterpenes; D042461:Vascular Endothelial Growth Factor A; C030419:andrographolide
keywords: Andrographolide; Angiogenesis; Zebrafish