Searching for a chemopreventive agent is an important approach for breast cancer management. This study was aimed to evaluate the chemopreventive potential of Ulmus Pumila leaves extract on breast tumorigenesis induced in experimental animals by N-methyl-N-nitrosourea (MNU). This target was undertaken through preparing several extracts from the fresh leaves of Ulmus pumila using different solvents against MCF-7 breast adenocarcinoma cell line. Our in vitro results demonstrated that the methanolic extract of Ulmus pumila (UPME) showed the highest cytotoxic activity against the growth of MCF-7 cells. After determination of UPME safe dose (1/10) of a lethal dose, a total of 90 female Wistar rats were divided into six groups; normal control group, UPME-treated group, tumor group, prophylactic group, protective group and therapeutic group. At the end of the experiment, the biochemical and histopathological investigations were carried out. The results revealed that UPME treatment significantly decreased the activities of liver enzymes, kidney function, cancer antigen 15-3 (CA 15-3) level, urokinase plasminogen activator (uPA), heparanase (HPA), basic fibroblast growth factor (bFGF), B-cell leukemia lymphoma 2 (Bcl-2) and cyclooxygenase-2 (Cox-2).
By contrast total antioxidant capacity (TAC) was increased in therapeutic, protective and prophylactic groups as compared to tumor group. These improvements were supported with histopathological changes, indicating the chemotherapeutic potential of UPME through the inhibition of angiogenesis, proliferation, metastasis and the activation of apoptosis.
Key words: Ulmus pumila, Breast cancer, Angiogenesis, Metastasis, Apoptosis.
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