الفهرس 
contentsOnly 14 pages are availabe for public view
 |  | from | 167 |  |  |
| | | from | 167 | | |
Abstract
Natural phytochemicals are well known by their potentials for preventing oxidative stress as potent scavengers of free radicals and by modulating the activity of anti-oxidant enzymes (Lobo et al., 2010). Moreover, the phytochemicals anti-tumor activity via diminishing the inflammatory and oncogenic signaling pathways was discussed by several literatures (Mann et al., 2009). The present study aimed to assess the effect of a commercial product of seven phytochemicals in combination (BSG) on the treatment and gaining control over the spread and growth of solid tumor of Ehrlich cells in an in vivo model of breast cancer. In the present study, mice were randomly assigned into four groups after been acclimatized to normal laboratory conditions for two weeks. •group I: untreated mice served as (control group). •group II: mice orally given a daily dose of BSG (1g/kg. b.w) for 2 weeks (BSG Group). • group III: injected once subcutaneously by Ehrlich cells (3x106) to induce Ehrlich solid tumor (Eh. group). • group IV: injected once subcutaneously by Ehrlich cells (3x106) to induce Ehrlich solid tumor. After 2 weeks of injection (till tumor appears) then mice were orally given a daily dose of 1g/kg. b.w. of BSG for 2 weeks (Eh.+ BSG group). At the end of experiment mice were anaesthetized after overnight fasting for 12 hrs, mice were then dissected and blood samples were collected from the heart by cardiac puncture from all groups, while tumors were collected from groups III and IV. The physical examination of tumors volume at both groups (III and IV) indicated a significant reduction of tumors volume in group IV in comparison to (group III of untreated Eh. Cells). Meanwhile, no changes at mice survival and body weight were recognized. BSG dependent reduction at the tumor volume in group IV was confirmed via evaluating the effect of the BSG on the expression of tumor progression markers CEA and TNFα. The data revealed a significant effect of the BSG on diminishing the expression of both CEA and TNFα. To determine the oxidative stress status of all studied groups, levels of RS, antioxidant enzymes and oxidative stress markers in blood plasma were estimated. The data elucidated the direct effect of Ehrlich tumor (group III) in upregulating RS and downregulation of antioxidant enzymes generations which was determined by significant increase at H2O2 and NO and reduction at expression of SOD, CAT, GPx and GSH, respectively. The impact of this oxidative stress status on lipid peroxidation was determined via a significant induction at percentage of MDA. Blood picture analyses revealed a significant impact of tumor development in upregualting the percentage of WBCs and downregulation of RBCs count and Hb content in comparison to control group. In group IV, the present studies showed a profound effect of BSG in overcountering the impact of tumor development in upregulating the overall body oxidative stress. The data illustrated significant effects of BSG in downregulating H2O2, NO generation and incidence of lipid peroxidation by reduction of percentage of MDA. Meanwhile, the two weeks BSG treatment upregulates the expression of antioxidant enzymes SOD, CAT, GPx and GSH in comparison to Ehrlich group. Blood samples analyses showed a significant effect of BSG in contradicting the Ehrlich dependent upregulation at WBCs and the downregulation at RBCs counts and Hb content. Flow cytometric analyses for the tumor cell cycle and annexin V expression revealed a significant effect of BSG treatment in induction of cell cycle arrest and cell apoptosis, respectively. For further analyses of the effect of BSG on tumor progression Immuno-localization of markers of cell proliferation, apoptosis and angiogenesis; using elisa and immunohistochemical approaches was conducted. The resulting data illustrated a significant BSG dependent inhibition of Ki67 and VEGF as markers of cell proliferation and angiogenesis, respectively. In order to elucidated the molecular signaling implicated in BSG dependent induction of cell apoptosis immunohistochemical labelling of tumor tissues of group III revealed a significant inhibition of P53 expression. Meanwhile, tumors of group IV showed a marked P53 staining elucidating the effect of BSG treatment in restoring wild type P53 expression in tumor tissue. As a result of P53 activation, marked induction of P53-dependent cell apoptosis in BSG treated tumors of group IV was recorded which was indicated by an upregulation at Bax and downregulation at Bcl2 expressions. Conclusion: Relying on the above stated data we can conclude that BSG has a remarkable effect on inhibition of Ehrlich cells growth and tumor development via targeting several signaling pathways that promoted tumor proliferation, angiogenesis and survival. Extra evidences were provided for the role of BSG in maintaining the redox balance in both tumor tissue and blood plasma via free radical scavenging and anti-oxidant enzymes upregulation. These preliminary results augment the need for prospective studies of BSG on targeting other types of cancer. In addition, the absence of toxic side effects of BSG in cancer therapy would help in speeding the transition of our results from lab to clinical applications.