Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

Although Tamoxifen (TAM) is one of the most widely used drug in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells and Ehrlich tumor bearing mice. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with down-regulation of Bcl-2 and Beclin 1 levels. However, the ratio between microtubule associated protein light chain 3 - II and -I was not altered. Vascular endothelial growth factor level was also decreased, whereas, levels of glutathione and nitric oxide were increased. Similarly, TAM+CAPE increased the life span of tumor bearing animals and caused a marked regression in their tumor size and weight compared to those treated with TAM alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials. This effect provides a rationale for further investigation of this combination

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