Abstract
The aim of this study was to investigate the inhibition effects of cordycepin and its derivatives on endometrial cancer cell growth. Cytotoxicity MTT assays, clonogenic assays, and flow cytometry were used to observe the effects on apoptosis and regulation of the cell cycle of Ishikawa cells under various concentrations of cordycepin, cisplatin, and combinations of the two. Validated in silico docking simulations were performed on 31 cordycepin derivatives against adenosine deaminase (ADA) to predict their binding affinities and hence their potential tendency to be metabolized by ADA. Cordycepin has a significant dose-dependent inhibitory effect on cell proliferation. The combination of cordycepin and cisplatin produced greater inhibition effects than did cordycepin alone. Apoptosis investigations confirmed the ability of cordycepin to induce the apoptosis of Ishikawa cells. The in silico results indicate that compound MRS5698 is least metabolized by ADA and has acceptable drug likeness and safety profiles. This is the first study to confirm the cytotoxic effects of cordycepin on endometrial cancer cells. This study also identified cordycepin derivatives with promising pharmacological and pharmacokinetic properties for further investigation in the development of new treatments for endometrial cancer.