Development of a clinical application of Cordyceps sinensis as an antimetastatic agent utilizing the properties of its active ingredient

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We demonstrated that cordycepin (3'-deoxyadenosine) is an active ingredient of water extracts of the fruiting bodies of cultured Cordyceps sinensis (WECS). In the first year of this project, I investigated the adjuvant effect of 2'-deoxycoformycin (DCF), an adenosine deaminase inhibitor, on the antitumor actions of WECS and cordycepin using mouse B16-BL6 melanoma and Lewis lung carcinoma cells in vitro. As a result, DCF at 5 μM reinforced the antitumor effect of WECS and cordycepin, three and three hundred-fold, respectively. DCF alone at 5 μM was wholly ineffective on the growth curves of both cell lines. In the second year of this project, we evaluated the antimetastatic effect of WECS on a spontaneous metastatic mouse model, prepared by inoculation with B16-BL6 cells into the footpad of the right hind leg. Two weeks after inoculation, the primary tumor was completely resected. DCF (0.05 mg/kg) alone or DCF plus WECS (10 mg/kg) administered intraperitoneally for one week after tumor inoculation and for one week after primary tumor resection did not prolong the survival of model mice, while WECS (10 mg/kg) alone administered intraperitoneally for the same, duration significantly prolonged mouse survival compared with that of control mice, as shown on Kaplan-Meier analysis. Survival time of control mice was less than 53 days in all cases, while three of six mice that were administered WECS (10 mg/kg) survived over 110 days. None of the mice administered WECS (10 mg/kg) showed adverse systemic effects. WECS at 3 mg/kg did not show any antimetastatic action, while WECS at 100 mg/kg significantly reduced the body weights of mice as an adverse effect. In conclusion, after removing its inactive components, WECS should be a candidate for clinical use as an antimetastatic agent.