Anti-proliferative and anti-angiogenic activities of ion-channel modulators: In-ovo, in-vitro and in-vivo study
Journal Title: Asian Pacific Journal of Tropical Biomedicine - Year 2017, Vol 7, Issue 6
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 mM of 4-AP and 7 mM 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.
Authors and Affiliations
Chandana Kamili, Ravi Shankar Kakataparthy, Uma Maheshwararao Vattikutti, Vijay Chidrawar, Sindhuri Ammineni
Keywords
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- EP ID EP254515
- DOI 10.1016/j.apjtb.2017.05.005
- Views 93
- Downloads 0
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