Breast cancer is the most common cancer among women in the world and the incidence is increasing alarmingly. It was aimed to determine the effect of raloxifene (RAL) and fluoxetine (FLX) on selected parameters in 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced mammary carcinoma. Thirty‐two female Wistar albino rats were assorted into four groups: DMBA (group I), DMBA+RAL (group II), DMBA+FLX (group III), and DMBA+RAL+FLX (group IV). Mammary tissue vascular endothelial growth factor (VEGF), macrophage colony‐stimulating factor (M‐CSF), matrix metalloproteinase‐9 (MMP‐9), and tissue inhibitors of matrix metalloproteinase‐1 (TIMP‐1) levels were determined by the enzyme‐linked immunosorbent assay method. The tissue VEGF levels were lower in group IV compared with DMBA group. Decreased M‐CSF levels were observed in all therapeutic groups rather than the DMBA group, but the most effective decrease was found in group IV. Compared with the DMBA group, MMP‐9 levels were statistically significantly decreased in group II and group IV. However, TIMP‐1 levels were higher in the whole therapeutic groups rather than the DMBA group and the most effective increase was observed in group IV. Results of the present study suggest that combined therapy of RAL with FLX might lead to a better outcome targeting breast tumor.

Abstract:The present study investigated the potential chemoprevention effects of Tangeretin (TAN) and Pomegranate (PE), both alone and in combination, on the oxidant-antioxidant status in 7,12-dimethylbenz [a] anthracene (DMBA)-evoked rat mammary carcinogenesis. Fifty-six female Sprague Dawley rats were divided into eight groups: Group I was control, Group II, III and IV were treated with pomegranate, tangeretin and pomegranate+tangeretin, respectively. Group V was DMBA-induced breast cancer-bearing rats, Group VI, VII and VIII also received simultaneously pomegranate, tangeretin and pomegranate+tangeretin, respectively, and also received a single dose of DMBA. The levels of malondialdehyde (MDA), as well as antioxidant enzyme activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured in the plasma samples of rats. The plasma MDA level was found statistically significant higher in DMBA group (p = 0.001) and decreased significantly in all chemoprevention groups (p < 0.005). Plasma CAT, GPx, SOD activities were found decreased in Group V respect to control group. However; it was observed increases in whole prophylactic groups in respect to Group V. The most increases were found in Group VIII (for all enzyme activities). It was suggested that combination of Tangeretin and Pomegranate might have protective effect against DMBA-induced oxidative stress in breast cancer-bearing animals.