Apoptosis and receptor-mediated signal regulation of cultured tumors by glycoprotein from Meretrix lusoria

In dietary shellfishes, we found that the hot water extract of hard clam (Meretrix lusoria) showed immune bioactivity remarkably. It was clarified that the principle induced cell proliferation of mouse spleen cells, T cell lines, macrophages and human peripheral blood mononuclear cells, and also enhanced immuno lobulin secretion in human hybridoma cell lines. In this report, we showed the mechanisms for antitumor effects of the principal S75 II. Cell viability was quantified by MTT assay, and apoptosis was determined by both PI staining and DNA fragmentation. Tumor cells treated with S75 H (10 mug/ml for 24h) exhibited patterns of apoptotic cell death. Tumor cells pretreated with swainsonine, a alpha-mannosidase H inhibitor, the apoptosis-inducing activity was blocked significantly. In the presence of caspase inhibitor z-VAD-fmk partially rescue cell viability, implying that apoptosis occurrence via the activation of caspase family. Our results suggest that the principle of Meretrix lusoria may be a novel sialic acid-binding lectin, and its antitumor effects was probably through caspase related apoptosis mediated by cell membrane glycosyl-moiety interaction.