The IGF/IGF-1R pathway including the IGF, IGF-1R, and IGFBPs proteins, plays an important role in the growth and survival of Ewing family tumors. In general, activation of IGF-1R results in intramolecular receptor autophosphorylation and phosphorylation of critical downstream targets. This leads to activation of several signaling pathways, including the PI3K/Akt pathway and the Ras/MAPK pathway, which results in activation of specific genes for cell survival and proliferation. Therefore, development of the therapeutic way for the effective inhibition of IGF-1R signal pathway may provide a promising strategy for the prevention and treatment of Ewing sarcoma tumors. It has been reported that in several tumors EGCG, the major biologically active component of green tea, inhibits activation of the RTKs such as EGFR, HER2, HER3, and IGF-1R. Cascadely it is associated with inhibition of multiple downstream signaling pathways for cell survival and proliferation. In this study, we determined the growth inhibitory and pro-apoptotic properties of EGCG on Ewing sarcoma tumors. Our data demonstrated that a treatment of EGCG resulted in a significant inhibition of the growth and viability of the Ewing tumor cell lines. EGCG treatment resulted in a significant inhibition of the activation of IGF-1R. As evident from BrdU incorporation experiments, EGCG treatment to the cells was found to result in significant inhibition of cell proliferation and dramatic increase of apoptosis. In addition, EGCG treatment caused the deactivation of Akt and MEK. In contrast, when we treated EGCG on HBMEC (Human Brain Microvascular Endothelial Cells) we could not see any effects on cell antiproliferation and proapoptosis. So we think the effects of EGCG are very specific to tumor cells. Based on this study, we suggest that EGCG could be developed as a chemopreventive agent or as a treatment therapy for the management of Ewing sarcoma. However, detailed mechanistic in vitro and in vivo studies are needed to further evaluate the anti-tumor efficacy of EGCG in appropriate culture and animal models.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA