Abstract
Integrin-linked kinase (ILK) is a member of Ser/Thr kinase which interacts to the cytoplasmic domain of β-integrins, and thereby induces apoptosis. ILK is considered as potential drug target because it's direct involvement in the tumor progression. Here, we have performed molecular docking followed by 100 ns MD simulation to understand the mechanism of interaction of ILK with the ellagic acid (EA). EA is well known for its antiproliferative and antioxidant properties in cancer cell lines and animal models. We have observed that EA binds to the active site cavity of ILK and causes conformational changes in the ILK structure. The orientation of EA in the active pocket of ILK showed to have least RMSD values and stable. The average binding energy ILK-EA complex calculated during MMPBSA was −191.267 kJ/mol, indicating a relatively strong binding affinity. The actual binding affinity of EA to ILK was measured by fluorescence spectroscopy and Kb and n values were 9.28 μM and 1.9264 (~2), respectively. The IC50 values for EA were 26.22 ± 0.12 μM for MCF-7 and 38.45 ± 2.42 μM for HepG2 cells, estimated by MTT assay. Our findings are helpful to design EA-based novel inhibitors of ILK which have potential to attenuate tumor progression.