Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells

Cordyceps militaris is a well-known Chinese traditional medicinal mushroom frequently used for tonics and recently of a potential interest for cancer intervention. Here, we explored the cancer cell killing activity of the hot water extracts of C. militaris cultured mycelia (CMMY) and cultivated fruiting bodies (CMFB). We found that CMFB exhibited a greater cytotoxic effect against various cancer cells over CMMY. Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by CMFB treatment but only slightly induced by same concentration of CMMY treatment in human HL-60 leukemia cells. Cordycepin in CMFB (10.47 mg/g) is significantly higher (∼15.2 times) than that of CMMY (0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of CMMY and cordycepin. By complementing cordycepin into CMMY to the level comparable with CMFB, we observed that CMMY (500 μg/ml) with cordycepin (4.8 μg/ml) induced apoptosis to a level similar to that induced by CMFB (500 μg/ml). Together, our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells and therefore explaining a better anti-proliferating activity of CMFB over CMMY.