Chemotherapeutic effect of Ulmus pumila leaves methanolic extract against N-methyl-N-nitrosourea-induced mammary carcinoma in female rats: An in vitro and in vivo study

ABSTRACT

Searching for a chemopreventive agent is an important approach for breast cancer management. The aim of the study was to evaluate the chemopreventive potential of Ulmus pumila (UP) leaves extract on breast tumorigenesis induced in experimental animals by N-methyl-N-nitrosourea. This target was undertaken through preparing several extracts from the fresh leaves of UP using different solvents against the breast adenocarcinoma cell line (MCF-7). Our in vitro results demonstrated that the methanolic extract of UP (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, the in vivo 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, heparanase, basic fibroblast growth factor, B-cell leukemia lymphoma 2, and cyclooxygenase-2. By contrast, total antioxidant capacity (TAC) was increased in therapeutic, protective, and prophylactic groups as compared to the tumor group. These improvements were supported with histopathological changes. These results indicated that the chemotherapeutic potential of UPME through stimulation of apoptosis and the suppression of angiogenesis, proliferation, and metastasis.