Antitumor Effects of MRS5698, a Cordycepin Derivative, on Endometrial Cancer Cells

Abstract

Endometrial cancer drug treatments often produce undesirable effects. Thus, discovering new drugs with fewer side effects is required. Cordycepin is a constituent of Cordyceps sinensis, which has been proven to inhibit tumor growth by stimulating the adenosine A3 receptor (A3R). However, cordycepin is rapidly degraded by adenosine deaminase (ADA) and has a clinically unacceptable short half-life. One of its derivatives, MRS5698, was predicted to exhibit antitumor effects with a poor affinity to ADA by our previous validated in silico experiments. The purpose of this study was to explore the possibilities of using MRS5698 as a novel antitumor agent through experiments on Ishikawa and HEC-1A cells. The detection of inhibition and apoptotic rate of MRS5698 and cisplatin, and their combination, on Ishikawa and HEC-1A cells were performed by MTT assays and flow cytometry, respectively. The inhibition rates of MRS5698 on Ishikawa and HEC-1A cells were both significantly higher than the control groups ( P < 0.05). MRS5698 produced a higher inhibitory effect on HEC-1A cells than on Ishikawa cells with IC50 values of 20.55 and 27.25 μg/mL, respectively. MRS5698 had a stronger inhibitory effect than cisplatin on HEC-1A cells. The Annexin V-FITC/propidium iodide assays demonstrated that the total rate of apoptosis of MRS5698 on HEC-1A cells was higher than that on Ishikawa cells. The results of MTT assay and cellular apoptosis showed that the combined use of MRS5698 and cisplatin produces dose-independent antagonistic effects. MRS5698 produced antitumor effects on both cell lines, which were better than that of cordycepin. However, the combined use of MRS5698 and cisplatin produced an antagonistic effect. A further in vivo study could be considered for investigating the antitumor effects of either MRS5698 monotherapy or MRS5698 in combination with other nonplatinum-based chemotherapeutic drugs in treating endometrial cancer.