Insights from diversified anti-angiogenic models: Role of b-interferon inducer DEAE-Dextran

Abstract

Background: Angiogenesis, the physiological process involving growth of new blood vessels from preexisting vessels, is essential for organ growth and repair. However, the imbalance in angiogenesis contributes to copious pathologies including cancer. Preceding the development of anti-angiogenic or proangiogenic agents, its evaluation is equally imperative; hence, precise and adequate models required. Valid mammalian models are expensive, time-consuming and not easy to set up, instigating legal and ethical aspects making it necessary to establish models with satisfactory activity and limited drawbacks. Methods: We investigated the activity of DEAE-Dextran on diversified models viz. in vitro cell migration assay, ex vivo aortic ring assay, in vitro chick yolk sac membrane assay and in vivo matrigel plug xenograft model corroborating its anti-angiogenic potential and establishing the best means of evaluation. Results: Assorted models were reproducible and correlative to one another. DEAE-Dextran exhibited excellent anti-angiogenic effect in cell migration assay over a duration of 24 h compared to the vehicle control fibroblast cell line and aortic ring possessed an alleviated rate of sprouting when treated with DEAE-Dextran with contrast to vehicle control aorta. Similarly, decreased vascular density was observed in DEAE-Dextran treated chick embryos implicating potency of the b-interferon inducer. Augmenting to these results, the matrigel plugs also mitigated vascular net as well as reduced levels of angiogenic marker CD31. Conclusion: Substantially, DEAE-Dextran leads to anti-tumor activity through anti-angiogenic action and a combination of in vitro and in vivo model is vital for the judgement of anti-angiogenic potential since an in vitro model exempts mammalian-culture considerations.