الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 84 |  |  |
| | | from | 84 | | |
Abstract
Breast cancer is one of the most two common causes of death in women worldwide, as well as its harmful influence on their psychological state during therapy. Millions of diagnosed breast cancer cases are reported every year with a high mortality rate practically in devolving countries. On the other hand, Sorafenib (SOR), a small multikinase inhibitor, has become a systematic drug for treating a variety of cancer diseases including breast cancer. SOR increases the survival of cancer patients; however, its efficiency is not ideal and needs further development. Therefore, in the present work we purified a short glycoprotein isolated from natural honey and tested the regulatory role of this extract (H-P) on breast cancer cells compared with the effect of the anticancer drug, Sorafenib (SOR), using MCF-7 cells. Furthermore, we investigated the interaction between Raf-1 activation and autophagy autophagic process as potential targets of Sorafenib (SOR), and H-P extract. Interestingly, the treatment with H-P showed competitive regulation of phosphorylated Raf-1 and matched autophagy-related LC3B compared with SOR treatment. The combination of SOR and H-P extract showed a strong reduction of Raf-1 and LC3B with minimum detectable proinflammatory cytokines. This regulation of the cytokine secretion by H-P extract and its combination with SOR resulted in decreasing the expression of the transcription factor NF-kB in treated cells. Moreover, the transfection of MCF-7 cells with siRNA antagonist Raf-1 expression markedly decreased the expression of LC3B, while increased the expression of NF-kB1 and NF-kB2. However, the transfection with siRNA for down-regulation Atg12 failed to affect the expression of Raf-1, but the expression of NF-kB effectors was increased. Collectively, these findings suggest that H-P -mediated Raf-1, LC3B, and NF-kB provides a novel multi-kinase inhibitor which also contributes to enhancing the efficiency of SOR in treating MCF-7 cells. Additionally, we confirm the regulatory role of Raf-1 in the regulation of autophagic machinery, as a potential downstream target, by controlling the expression of its mediator LC3B.