Specific Killing of Multiple Myeloma Cancer Cells by Epigallocatechin-3-Gallate Extracted from Green Tea.

Epidemiological studies have demonstrated chemopreventive effects of green tea in several types of cancers. The active ingredient present in green tea, and not black tea, is epigallocatechin-3-gallate (EGCG). EGCG has been shown to interfere with multi-step carcinogenesis and it exerts its effects in pharmacologically attainable non-toxic concentrations. We examined the effects of EGCG on growth of MM cells. We observed dose- and time-dependent induction of apoptosis in MM cells following EGCG treatment. Apoptotic cell death, as measured by annexin V labeling was 38 ± 6% and 60 ± 8% at 24h with 100 mM and 200 mM EGCG concentration, respectively. This increased to 73 ± 5% and 88 ± 2% at 72h, respectively. Importantly, no significant apoptosis was observed in normal cells exposed to 200 μM EGCG. The apoptotic cell death was predominantly caspase 9 dependent and not caspase 8 dependent as evaluated using specific caspase 8 and 9 inhibitors. The anti-tumor effects of EGCG has been demonstrated to be mediated via a metastasis-associated 67-kDa laminin receptor. Gene expression profile of MM cell lines (n=6) and patient myeloma cells (n=15) compared to normal plasma cells (n=3) showed 3.1 ± 1 and 3.9 ± 0.7-fold elevation of laminin receptor respectively. Significant upregulation of this receptor was observed in 6 of 6 MM cell lines and 14 of 15 MM patient samples. We are currently investigating possible role of laminin receptor in EGCG mediated cell death in MM and combinations that may enhance EGCG-mediated MM cell death. These data suggest EGCG as a promising natural agent with excellent therapeutic index.