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

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) and4-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 10-5M and 10-4M 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 m M of 4-AP and7 m M 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.