Abstract 953: Benzyl isothiocyanate suppresses pancreatic cancer angiogenesis and invasion by inhibiting Akt and MMP-2

We have shown in our previous studies that benzyl isothiocyante (BITC) suppress the growth of pancreatic cancer cells by inhibiting the activation of NF-kB and STAT-3 without affecting the viability of normal HPDE cells. Further, we demonstrated that oral administration of BITC significantly blocked the growth of pancreatic tumor xenografts in vivo. In the present study, we examined the effect of BITC on pancreatic cancer angiogenisis and invasion. Our results demonstrate that 5-10µM BITC almost completely blocked neovasculture formation in an ex vivo chick chorio-allantoic membrane (CAM) model. In agreement with these results, in vivo matrigel plug assay in athymic nude mice also reveal that the hemoglobin content in the implanted matrigel plug was reduced by 70% in the mice which were orally fed 12µmol BITC for 7 days as compared to controls, suggesting reduced blood vessel formation. In a matrigel tube formation assay using mouse brain endothelial cells, BITC treatment significantly inhibited VEGF-induced tube formation. As compared to controls, 5µM BITC treatment for 36h caused a drastic reduction in the number of cells that migrated into the wounding area in a wound healing assay. Our results also showed that the tumor cell invasion was effectively (p