Green tea (-)-Epigalocatechin-3-gallate inhibits KIT activity and causes caspase-dependent cell death in gastrointestinal stromal tumor including imatinib-resistant cells

Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for gastrointestinal stromal tumor (GIST) patients.  Unfortunately, most patients responding to imatinib will eventually exhibit the resistance, the cause of which is not fully understood.  The serious clinical problems of imatinib-resistance demand alternative treatment strategy.  (-)-Epigallocatechin-3-gallate (EGCG), a main component of green tea catechin, has been demonstrated potential anti-tumor effects on various types of cancer cells.  Here, we report for the first time that EGCG has shown anti-tumor effects on gastrointestinal stromal tumor (GIST) cell line GIST-T1 by suppressing cell proliferation and eventually inducing cell death via caspase-dependent pathways.  GIST-T1 and imatinib resistant GIST-T1 (GIST-T1 IR) cells were used to assess the effects of EGCG.  In both cell types, KIT activity was completely inhibited after 4 hour treatment with 60 μM EGCG.  EGCG specifically inhibited activated KIT,...