Cordyceps militaris is a medicinal fungus, which has been used for patient suffering from cancer in Oriental medicine. It was previously reported that C. militaris extracts are capable of inhibiting tumor growth, however, the anti-poliferative effects of human cancer cells have not been poorly understood. In this study, to elucidate the growth inhibitory mechanisms of human cancer cells by treatment of aqueous extract of C. militaris (AECM) we investigated the anti-proliferative effects of AECM in A549 human non-small-cell lung cancer cells. Exposure of A549 cells to AECM resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay. The antiproliferative effect by AECM treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. AECM treatment induced G2/M arrest of the cell cycle and the levels of tumor suppressor p53 as well as cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in a concentration-dependent manner. Taken together, these findings suggest that AECM-induced inhibition of A549 cell proliferation is associated with the induction of cell cycle arrest at G2/M phase via induction of p53 and p21, and C. militaris may have therapeutic potential in human lung cancer. (Cancer Prev Res 12, 273-280, 2007)

Keywords: Cordyceps militaris, A549, G2/M arrest, p53, p21