Ganoderma lucidum, a traditional Chinese medicinal fungus, has been a favourite remedy in oriental medicine for centuries. The objective of this study is to analyze whether G. lucidum affects cancer cell proliferation and cell death. Malignant human breast carcinoma cells were used in our studies. Different preparations of G. lucidum spores were added to the cancer cells at a final concentration of 1 mg/ml followed by incubation of the cultures for two days. Treatment with G. lucidum resulted in tumour cells detachment from the tissue culture plates and death. The proliferation of the adherent cells was also inhibited. The experiments indicated that the inhibitory effects of G. lucidum on cancer cell growth were sporoderm-broken spores (broken by enzymatic method) > sporoderm-broken spores (broken by physical method) > intact spores > buffer control. The polysaccharides isolated from G. lucidum cultivated with wood-logs exhibited the greatest inhibitory effect on cell proliferation, which was concentration-dependent. These results were confirmed by trypan blue staining and MTT assay. The inhibitory effect of G. lucidum on cell proliferation appeared to occur through the Erk pathway: The expression of Erk was reduced in the presence of G. lucidum polysaccharide. (c) 2006 Elsevier Inc. All rights reserved.