Anti-proliferative and anti-angiogenic activities of ion-channel modulators: In-ovo, in-vitro and in-vivo study

Abstract

Objective: Angiogenesis is the development of new blood vessels. The ion channels on endothelium play a vital action in cell proliferation and so in the related angiogenesis. We aimed to investigate the anti-angiogenic effects of Mefloquine (Cl− channel blocker) and 4-Aminopyridine (K+ channel blocker). Methods: The anti-angiogenic activities of Mefloquine and 4-Aminopyridine (4-AP) were investigated by in-vivo (sponge implantation method), in-vitro (aortic ring assay) and in-ovo (CAM, Chick Chorioallantoic membrane) methods. The standard antiangiogenic drug used was Bevacizumab. Results: In the CAM assay, both the ion channel blockers exhibited noticeable antiangiogenic activity at the concentrations of 10−5 M and 10−4 M where they significantly exhibited ant proliferative activity by inhibiting the new blood vessel formation. For the further confirmation anti-angiogenic activity was evaluated in vitro and in vivo. In Rat aortic ring assay reduction in the area of sprouts were observed with 40 μM of 4-AP and 7 μM of Mefloquine. A significant reduction in weight of sponges, number of blood vessels formed and hemoglobin content were observed at 4.2 mg/kg of 4-AP and 20 mg/kg and 30 mg/kg of Mefloquine. Conclusions: These scientific findings indicate the use of Mefloquine and 4-Aminopyridine in pathological situations involving excessive angiogenesis. Negative regulation of cell volume, cell migration and proliferation of blood vessels may be the underlying molecular mechanisms.

Keywords

• Ion-channels
• Sponge implantation method
• Aortic ring assay
• Chick Chorioallantoic membrane