The mechanism of cell cycle arrest of tumor cells induced by ganoderic acid Me (GA-Me) is not understood. In this work, GA-Me was found to possess remarkable cytotoxicity on highly metastatic lung carcinoma 95-D cell line in both dose- and time-dependent manners. The effect of GA-Me on cell cycle arrest was found in 95-D, p53-null lung cancer cells H 1299, HCT-116 p53(+/+) and HCT-116 p53(-/-) human colon cancer cells. To obtain an insight into the role of p53 in cell cycle arrest by GA-Me, 95-D, H1299, HCT-116 p53(+/+) and HCT-116 p53(-/-) cells were used for further investigation. GA-Me arrested cell cycle at G, phase in 95-D and HCT-116 p53(+/+) cells while 5 phase or G(1)/S transition arrest in H1299 and HCT-116 p53(-/-) cells. The results suggested that p53 may be a target of CA-Me, and it may be looked at as a new promising candidate for the treatment of carcinoma cells. (C) 2009 Elsevier Ltd. All rights reserved.