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

Abstract 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 (CM MY ) and cultivated fruiting bodies (CM FB ). We found that CM FB exhibited a greater cytotoxic effect against various cancer cells over CM MY . Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by CM FB treatment but only slightly induced by same concentration of CM MY treatment in human HL-60 leukemia cells. Cordycepin in CM FB (10.47 mg/g) is significantly higher (∼15.2 times) than that of CM MY (0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of CM MY and cordycepin. By complementing cordycepin into CM MY to the level comparable with CM FB , we observed that CM MY (500 μg/ml) with cordycepin (4.8 μg/ml) induced apoptosis to a level similar to that induced by CM FB (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 CM FB over CM MY .