To understand the hypocholesterolemic activity of green tea, our in vitro studies screened the relative efficacy of two structurally distinct green tea catechins, epicatechin (EC) and epigallocatechin gallate (EGCG), on apolipoprotein B-100 (apoB) and lipid production using a well established human hepatoma cell-line, HepG2, as the model system. This study showed that HepG2 cells pretreated with EC and EGCG for 8 h exerted a dose-dependent inhibitory effect on apoB secretion. Total protein and albumin synthesis and secretion were unaffected indicating the effects on apoB secretion to be specific. Under lipid-rich conditions, apoB secretion was markedly reduced by EGCG and to a lesser extent by EC at 50 microM. Mechanistic study showed that tea catechins inhibited apoB secretion via a proteasome-independent pathway as indicated by a lack of response to N-acetyl-leucyl-leucyl-norleucinal (ALLN), a proteasome inhibitor. The effect on apoB secretion was also found to be independent of lipid biosynthesis. In summary, the data suggest that EGCG in contrast to EC is a potent inhibitor of apoB secretion. The results indicate that the gallate moiety in the catechin molecule may result in a beneficial effect on lipid metabolism in terms of apoB secretion.