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

Shuntaro Tsukamoto, Keisuke Hirotsu, Motofumi Kumazoe, Yoko Goto, Kaori Sugihara, Takafumi Suda, Yukari Tsurudome, Takashi Suzuki, Shuya Yamashita, Yoonhee Kim, Yuhui Huang, Koji Yamada, Hirofumi Tachibana

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

EGCG[(-)-epigallocatechin-3-O-gallate], themajor 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. In the present study, we show that EGCG-induced apoptotic activity is attributed to a lipid-raft clustering mediated through 67LR (67 kDa laminin receptor) that is significantly elevated in MM(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. We also found that EGCG induces aSMase translocation to the plasma membrane and PKCδ (protein kinase Cδ) phosphorylation at Ser 664, which was necessary for aSMase/ceramide signalling via 67LR. Additionally, orally administered EGCG activated PKCδ and aSMase in a murine MM xenograft model. These results elucidate a novel cell-death pathway triggered by EGCG for the specific killing of MM cells.

Original languageEnglish
Pages (from-to)525-534
Number of pages10
JournalBiochemical Journal
Volume443
Issue number2
DOIs
Publication statusPublished - Apr 15 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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