The role of Colchicine on actin polymerization dynamics: as a potent anti-angiogenic factor

Abstract

Over the years, cancer research has focused on different strategies to discover drugs and therapies to treat the metastatic stage of cancer. This stage depends upon the type, and the cause of cancer. One of the central facts about any cancer invasion is the formation of new blood vessels that provide nutrients to these uncontrollably dividing cells. This phenomenon is called angiogenesis and is responsible for tumor progression and metastasis. Tumor angiogenesis is a sequential process wherein various angiogenic factors produced by tumor cells bind to receptors of endothelial cells. This stimulates the cytoskeletal protein, especially actin to reorganize themselves and undergo the process of canalization. The driving force for such membrane transformation is spatially and temporally-regulated by polymerization of submembrane actin filaments. So far, Colchicine has been studied for its effectiveness in controlling microtubule reorganization during cell division, but its role is far from understood on actin polymerization. In our current study, we report the effect of Colchicine on actin polymerization dynamics using biophysical analysis like Right light scattering (RLS), Dynamic light scattering (DLS), Circular dichroism (CD) analysis, Scanning electron microscopy (SEM) study. Isothermal titration calorimetry (ITC) and kinetic measurements. Isothermal titration calorimetry (ITC) indicates multiple site binding for colchicine with actin aggregates. We have checked the in vivo effect of colchicine using end3 cells of Saccharomyces cerevisiae. We also report the anti-angiogenesis activity of colchicine via ex-ovo chicken chorioallantoic membrane (CAM) assay. We predict the target site of binding for the drug by docking studies. Based on our findings, we suggest the ‘drug-repurposed’ function for colchicine as a potential anti-angiogenic candidate. Communicated by Ramaswamy H. Sarma