Inorganic selenite can be transformed into organic forms and bind to proteins and polysaccharides in Se-enriched submerged Ganoderma lucidum cultures. In the present study, a novel Se-containing polysaccharide, SeGLP-2B-1, was purified from the Se-enriched mycelia of G. lucidum and the antiproliferative activities against six human cancer cell lines were investigated. The Se content of SeGLP-2B-1 was 186.7 microg/g, which was 150-fold larger than that of the regular polysaccharide GLP-2B-1 (1.3 microg/g). SeGLP-2B-1 (1.06 x 10(6) Da) was composed of glucose, rhamnose, xylose, and galactose with a molar ratio of 1.000:0.652:0.443:0.227. SeGLP-2B-1 exhibited an approximately 10-fold stronger antiproliferative activity against six human cancer cell lines as compared to GLP-2B-1. Thus, Se is believed to play an important role in increasing the antiproliferative property of SeGLP-2B-1. These findings indicate that SeGLP-2B-1 may serve as a dietary Se supplement.