Green tea polyphenol EGCG induces lipid-raft clustering and apoptotic cell death by activating protein kinase C delta and acid sphingomyelinase through a 67 kDa laminin receptor in multiple myeloma cells.

摘要

EGCG ((--)-epigallocatechin-3-O-gallate), the major polyphenol of green tea, has cancer chemopreventive and chemotherapeutic activities. EGCG selectively inhibits cell growth and induces apoptosis in cancer cells without adversely affecting normal cells; however, the underlying molecular mechanism in vivo is unclear. This study shows that EGCG-induced apoptotic activity is due to a lipid-raft clustering mediated through 67LR (67 kDa laminin receptor) that is significantly elevated in multiple myeloma cells relative to normal peripheral blood mononuclear cells, and that aSMase (acid sphingomyelinase) is critical for the lipid-raft clustering and the apoptotic cell death induced by EGCG. It was also found that EGCG induces aSMase translocation to the plasma membrane and PKC delta (protein kinase C delta) phosphorylation at Ser664, which was necessary for aSMase/ceramide signalling via 67LR. Additionally, orally administered EGCG activated PKC delta and aSMase in a murine multiple melanoma xenograft model. These results elucidate a novel cell-death pathway triggered by EGCG for the specific killing of multiple melanoma cells.