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Anti-angiogenic and vascular disrupting effects of C9, a new microtubule-depolymerizing agent

Xuan Ren1, Mei Dai, Li-Ping Lin

  • 1Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

British Journal of Pharmacology
|March 24, 2009
PubMed
Abstract

Insights

C9, a novel microtubule-depolymerizing agent, demonstrates significant anti-angiogenic and vascular-disrupting effects. It effectively targets tumour vasculature by impacting endothelial cell function and signaling pathways.

Area of Science:

  • Oncology
  • Vascular Biology
  • Pharmacology

Background:

  • Tumor blood supply is crucial for growth, making tumor vasculature a key therapeutic target.
  • C9 is a novel synthetic agent that depolymerizes microtubules.

Purpose of the Study:

  • To investigate the anti-angiogenic and vascular-disrupting activities of C9.
  • To elucidate the mechanisms underlying C9's effects on tumor vasculature.

Main Methods:

  • Assessed microtubule depolymerization using surface plasmon resonance and immunofluorescence.
  • Evaluated anti-angiogenic and vascular-disrupting effects in vitro (endothelial cell assays) and in vivo (rat aortic ring, chick chorioallantoic membrane, Matrigel plug assays).
  • Examined signaling pathways (Raf-MEK-ERK and Rho/Rho kinase) using Western blots and Rho activation assays.

Main Results:

  • C9 inhibited endothelial cell proliferation, migration, and tube formation, and suppressed angiogenesis in multiple assays.
  • C9 induced microtubule disassembly and down-regulated pro-angiogenic Raf-MEK-ERK signaling.
  • C9 disrupted in vitro vascular networks and in vivo neovasculature perfusion, with effects mediated by the Rho/Rho kinase pathway.

Conclusions:

  • C9 exhibits potent anti-angiogenic and vascular-disrupting properties.
  • These activities are linked to altered endothelial cell morphology and function via Raf-MEK-ERK and Rho/Rho kinase signaling.
  • C9 represents a promising new microtubule-binding agent for targeting tumor vasculature.

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