Combretastatin A-4 efficiently inhibits angiogenesis and induces neuronal apoptosis in zebrafish

Shi, Y.W., Yuan, W., Wang, X., Gong, J., Zhu, S.X., Chai, L.L., Qi, J.L., Qin, Y.Y., Gao, Y., Zhou, Y.L., Fan, X.L., Ji, C.Y., Wu, J.Y., Wang, Z.W., Liu, D.
Scientific Reports   6: 30189 (Journal)
Registered Authors
Chai, Linlin, Gao, Yu, Gong, Jie, Liu, Dong, Qi, Jialing, Qin, Yinyin, Shi, Yunwei, Wang, Xin, Yuan, Wei
Angiogenesis, Chemical genetics, Drug safety, Phenotypic screening
MeSH Terms
  • Animals
  • Apoptosis/drug effects*
  • Central Nervous System/drug effects
  • Central Nervous System/metabolism
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Models, Animal
  • Morphogenesis/drug effects
  • Neovascularization, Pathologic/drug therapy*
  • Neovascularization, Pathologic/metabolism
  • Receptors, Notch/metabolism
  • Signal Transduction/drug effects
  • Stilbenes/adverse effects*
  • Tumor Suppressor Protein p53/metabolism
  • Up-Regulation/drug effects
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
27452835 Full text @ Sci. Rep.
Cis-stilbene combretastatin A-4 (CA-4) and a large group of its derivant compounds have been shown significant anti-angiogenesis activity. However the side effects even the toxicities of these chemicals were not evaluated adequately. The zebrafish model has become an important vertebrate model for evaluating drug effects. The testing of CA-4 on zebrafish is so far lacking and assessment of CA-4 on this model will provide with new insights of understanding the function of CA-4 on angiogenesis, the toxicities and side effects of CA-4. We discovered that 7-9 ng/ml CA-4 treatments resulted in developmental retardation and morphological malformation, and led to potent angiogenic defects in zebrafish embryos. Next, we demonstrated that intraperitoneal injection of 5, 10 and 20 mg/kg CA-4 obviously inhibited vessel plexus formation in regenerated pectoral fins of adult zebrafish. Interestingly, we proved that CA-4 treatment induced significant cell apoptosis in central nervous system of zebrafish embryos and adults. Furthermore, it was demonstrated that the neuronal apoptosis induced by CA-4 treatment was alleviated in p53 mutants. In addition, notch1a was up-regulated in CA-4 treated embryos, and inhibition of Notch signaling by DAPT partially rescued the apoptosis in zebrafish central nervous system caused by CA-4.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes