Interaction analysis of amygdalin and integrins: An in-silico study to investigate amygdalin effect on cancer metastasis

Abstract

Cancer is the abnormal condition in which the cells divide exponentially and can spread to other body parts and is known as cancer metastasis. The studies of molecular mechanisms involved in metastasis have huge importance. The most commonly applied therapy is chemotherapy which has many adverse effects on the overallwell-being of the patient. Growing need for the advent of natural compounds as anti-cancerous agents is emphasized on. Amygdalin is one such compound which is promoted as an anti-cancerous agent especially in case of metastasis. It is suggested that amygdalin affects integrin proteins in the cancerous cells and blocks the downstream signalling pathways involved in cancer metastasis. Integrins involved are reported to be α1β1, α2β1, α3β1, α4β1, α5β1 and αvβ3.In this study, we focused on finding the type of interaction between amygdalin and integrin proteins, which are responsible for maintaining cell to cell contact and cell to ECM contacts necessary for adhesion, extravasation and migration and also to elucidate the amino acids of integrin proteins involved in the interaction with amygdalin. Docking of amygdalin and integrins was done after the modelling, energy minimization, protein quality assessment and active binding site assessment of integrin proteins using DogSiteScorer. Analysis of docking results was done online by PLIP (protein-ligand interaction profiler). We found out that there is a good binding affinity between amygdalin and integrins and the types of interactions like H-bonding and hydrophobic interactions elucidated the same and the amino acids involved were found out. The amino acids highlighted in this study are crucial for amygdalin binding to these proteins and if the amino acids get mutated in the integrin proteins amygdalin might not be able to bind effectively to the integrin proteins. Hence amygdalin prevents the downstream signalling pathways involved in cancer metastasis by binding to these integrins and thus it can be used as an anti-cancer agent against cancer metastasis.