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Biological and anti-vascular activity evaluation of ethoxy-erianin phosphate as a vascular disrupting agent

Wenshuang Yuan1,2, Chang Su1, Xiaotong Yang2

  • 1Department of Surgery, Minhang Hospital, Fudan University, Shanghai, People's Republic of China.

Journal of Cellular Biochemistry
|May 22, 2019
PubMed

Insights

Ethoxy-erianin phosphate (EBTP) shows significant anti-cancer effects by inhibiting cell proliferation and migration. This novel vascular disrupting agent is more effective and less toxic than combretastatin A-4P (CA4P).

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Combretastatin A-4P (CA4P) is a known vascular disrupting agent, but its toxicity limits clinical application.
  • Novel compounds are needed to target tumor vasculature and inhibit cancer progression effectively.
  • Indoleamine 2,3-dioxygenase (IDO) is implicated in tumor immune evasion and metastasis.

Purpose of the Study:

  • To evaluate the efficacy of ethoxy-erianin phosphate (EBTP) as a vascular disrupting agent.
  • To compare the antiproliferative and anti-migratory effects of EBTP with CA4P.
  • To investigate the impact of EBTP on IDO expression and related cancer cell behaviors.

Main Methods:

  • In vitro antiproliferative assays on various cancer and endothelial cell lines.
  • Cell cycle analysis (G2/M arrest) and wound-healing assays to assess migration.
  • In vivo studies including chorioallantoic membrane assay and Lewis lung carcinoma model in mice.
  • Western blotting to analyze IDO expression.

Main Results:

  • EBTP demonstrated significant antiproliferative activity against tumor cells and HUVECs at micromolar concentrations, with lower toxicity than CA4P.
  • EBTP induced G2/M phase arrest and inhibited HUVEC migration and tube formation.
  • EBTP suppressed IDO expression, consequently inhibiting IDO-induced migration and infiltration of 2LL-IDO cells and blocking vasculogenic mimicry.
  • In vivo studies showed high inhibition rates of Lewis lung carcinoma by EBTP.

Conclusions:

  • EBTP is a potent vascular disrupting agent with superior efficacy and reduced toxicity compared to CA4P.
  • EBTP's ability to inhibit IDO expression offers a dual mechanism for cancer treatment by targeting tumor vasculature and potentially overcoming immune suppression.
  • EBTP holds promise for the prevention and treatment of malignancies.
Keywords:
angiogenesiscombretastatin A4-phosphateethoxy-erianin phosphateindoleamine2,3-dioxyenasevascular disrupting agents

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