Antitumor activity of cordycepin in murine malignant tumor cell line: An in vitro and in silico study

Abstract

Cordycepin, also known as 3′-deoxyadenosine, is a substance similar to adenosine found in the entomopathogenic fungus Cordyceps militaris. This fungus is recognized for its remarkable therapeutic properties. This study seeks to investigate the antitumor activity of cordycepin in Dalton's lymphoma (DL) malignant cancer cell line using cytotoxicity and apoptosis as key parameters. Molecular docking (MD) and molecular dynamic simulation (MDS) were used to further validate the wet lab findings. Cytotoxicity study revealed that cordycepin induced significant cytotoxicity (P ≤ 0.05) in the DL cell line after 24 h of treatment. The efficacy of cordycepin as an apoptotic agent was substantiated by the highly promising results obtained through the apoptotic assay, utilizing the acridine orange/ethidium bromide (AO/EB) dual staining method. Cordycepin interacted with the active sites of antiapoptotic target proteins (BCL-XL, SURVIVIN, BCL-2, BCL-B, HSP90, and IAP1), as demonstrated by MD study that corroborated the findings of cytotoxicity and apoptotic assays. The comparative examination of docking outcomes indicated that cordycepin exhibits higher affinity for HSP90 in comparison to other targets. Molecular dynamics simulation for 120 ns further validated the findings of MD as cordycepin remained bound with HSP90 throughout the entire simulation time (120 ns) with favourable binding energy.