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Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
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Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

Published on: January 7, 2015

Deoxypodophyllotoxin exerts both anti-angiogenic and vascular disrupting effects

Zhenzhou Jiang1, Meijuan Wu, Jingshan Miao

  • 1Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.

The International Journal of Biochemistry & Cell Biology
|May 25, 2013
PubMed

Insights

Deoxypodophyllotoxin (DPT) shows potent anti-angiogenic and vascular disrupting effects, inhibiting tumor blood vessel formation and growth. This natural compound offers a promising strategy for novel anticancer drug development targeting tumor vasculature.

Area of Science:

  • Pharmacology
  • Cancer Biology
  • Molecular Biology

Background:

  • Tumor vascularization is crucial for solid tumor growth and metastasis.
  • Targeting tumor vasculature is a key strategy in anticancer drug discovery, employing anti-angiogenesis and vascular disruption.
  • Deoxypodophyllotoxin (DPT), a natural microtubule destabilizer, has potential anticancer properties.

Purpose of the Study:

  • To investigate the anti-angiogenic and vascular disrupting activities of deoxypodophyllotoxin (DPT).
  • To elucidate the mechanisms underlying DPT's effects on endothelial cells and tumor vasculature.

Main Methods:

  • In vitro assays: endothelial cell proliferation, migration, tube formation, capillary-like network disruption.
  • Ex vivo assays: rat aortic ring assay for angiogenesis inhibition and vascular disruption.
  • In vivo assay: chick chorioallantoic membrane assay for angiogenesis inhibition.
  • Molecular analysis: cytoskeleton reorganization, cell cycle arrest, protein expression (cyclin B1, p21), Rho/Rho kinase pathway.

Main Results:

  • DPT significantly inhibited endothelial cell proliferation, migration, and tube formation.
  • DPT demonstrated anti-angiogenic effects in rat aortic ring and chick chorioallantoic membrane assays.
  • DPT induced cytoskeleton reorganization and cell cycle arrest in endothelial cells at non-cytotoxic and higher concentrations, respectively.
  • DPT disrupted capillary-like networks in vitro and newly formed vessels in rat aortic rings, involving endothelial cell contraction via the Rho/Rho kinase pathway.

Conclusions:

  • Deoxypodophyllotoxin (DPT) exhibits significant anti-angiogenic and vascular disrupting properties.
  • DPT's mechanisms involve inhibiting endothelial cell functions, inducing cell cycle arrest, and disrupting vascular networks.
  • DPT represents a promising candidate for developing novel anticancer drugs targeting tumor vasculature.
Keywords:
Anti-angiogenesisDeoxypodophyllotoxinG2/M arrestMicrotubuleVascular disrupting effect

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