الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
The present work aimed to evaluate antitumor efficacy of rutin as a preventor and as a treatment on experimentally induced breast cancer
In female rats by using 7, 12-Dimethyl Benzanthracene (DMBA).
Sixty albino female rats weighted (120±10g) were equally divided randomly into the following 5 groups:
group 1 (control group), rats were gastric intubutric by gavage received daily 1ml saline for 21 days.
group 2 (rutin group), rats were gastric intubutric by gavage received daily 1 ml of rutin (50 mg/kg. bwt) for 21 days.
group3 (DMBA group), rats were gastric intubutric by gavage received daily (DMBA) (75 mg/kg. bwt) daily for 55 days.
group 4 (DMBA + rutin group) The treatment group: rats were gastric intubutric by gavage received DMBA (75 mg/kg. bwt) for 55 days, then received rutin (50 mg/kg. bwt) for 21 days.
group 5 (rutin + DMBA) The protective group: rats were gastric intubutric by gavage received rutin (50 mg/kg. bwt) for 15 days, then received rutin by gastric intubutric by gavage (50 mg/kg. bwt) and DMBA (75 mg/kg. bwt.) daily for 55 days.
Rats were sacrificed at the end of the experiment period and whole blood was collected by cardiac puncture from deeply ether anaesthetized rat. The separated serum samples were used for the assessment of alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, creatinine and urea, total antioxidant capacity (TAC), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6).
Whole mammary glands were isolated from each rat for the assay of caspase 3, CA15.3, HSP90, iNOS, NF-Kβ, ER-α, c-Src, were measured in 10% mammary gland tissue homogenates and for histopathological study.
The obtained results of the current work revealed that administration of DMBA resulted in significant elevations of ALT and ALP activities as well as urea and creatinine levels in an indicating manner of occurrence of damage to those internal organs (liver and kidney) which could be due to the produced reactive oxygen species by DMBA which also was manifested clearly in significant decrease of TAC content. In the same time administration of DMBA significantly elevated cytokines inflammatory parameters of interleukin-1β (IL-1B), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α).
In addition, DMBA significantly elevated tumor markers carcinoma antigen 15-3 (CA 15-3) and proto-oncogene tyrosine-protein kinase Src (Src) and upregulated gene expression of Estrogen receptor-α (ER-α) contributes to carcinogenesis and tumor progression as an oncogene. Qrt-PCR results of DMBA group indicated enhanced gene expression of nuclear factor κB (NF-κB), heat shock protein 90 (HSP 90) and inducible nitric oxide synthase (iNOS) pointing the stimulation of signaling pathway for cellular proliferation and progression.
Also, histopathological alterations in the architecture of the mammary glands were appeared clear in proliferative hyperplasia of the lining epithelial cells of the acini and lactiferous ducts with cystic dilatation as well as stratification.
Rutin administration to DMBA treated rats either as a protective agent or as a treatment showed significant amelioration of the investigated biochemical parameters which was manifested clearly in significant decreasing of the activities of ALT&ALP, levels of urea and creatinine indicating the reflection of the damage action induced by DMBA. Also, improving of antioxidant state occurred by increasing TAC levels.
Rutin intake as a protective or as a treatment also induced the apoptotic process by increasing of caspase-3 concentration and down regulation of NF-kB signaling pathway. Along with, anti-inflammatory activity presented in a significant decrease in inflammatory cytokines levels of IL-6, IL-1 β also TNF-α levels. Rutin significantly inhibited gene expression of HSP-90 and iNOS. Rutin showed anti-breast cancer activity and depresses cancer cell growth and survival through significant inhibition of tumor markers: CA 15-3 and c-Src with down regulation of ER- α indicating an anti-estrogenic effect of rutin for cancer management.
A mild recurrence of normal mammary gland tissue was histopathologically appeared by rutin intake as a protective and as a treatment agent, as there was improvement in the mammary structure with tumor regression