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Cordyceps militaris  is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of  C. militaris , the precise mechanism of  C. militaris  therapeutic effects is not fully understood. We examined the anticancer activities of  C. militaris  ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a  C. militaris -administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3 β  (p-GSK3 β ) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that  C. militaris  might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3 β -related caspase-3-dependent apoptosis.

Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model