Protective effectiveness of pomegranate extract and tangeretin on rat breast cancer model

Breast cancer, which is the most common type of cancer in women in Turkey as well as in the world, is still one of the most important health problems. In this study, it was aimed to investigate the protective effects of pomegranate extract and tangeretin, both alone and in combination, on a DMBA-induced rat breast cancer model. In this study, a total of 68 female rats aged 8-10 weeks were randomly divided into 8 groups. The first 4 groups were designed as the controls of cancer and treatment groups and were composed of the Control, Pomegranate (P), Tangeretin (T) and Pomegranate+Tangeretin (P+T) groups, respectively. The other 4 groups were designed as cancer and treatment groups and were composed of the DMBA (D) and DMBA+Pomegranate (D+P), DMBA+Tangeretin (D+T), DMBA+Pomegranate+Tangeretin (D+P+T) groups, respectively. Tumor markers and angiogenesis parameters were studied from plasma samples obtained from the rats sacrificed at the end of the 23-week treatment. In breast tissue samples, histopathological, immunohistochemical and Tunnel analyses, oxidant-antioxidant level measurements, and the expressions of specific proteins acting on apoptosis and cell cycle were performed. Histopathologically, while there was a 71.42 % incidence of tumor involvement in the DMBA group, it was determined that this ratio decreased in the treatment groups. While significant increases were observed in plasma CA15-3, CEA, VEGF, MMP-9 and NF-κB levels in the DMBA group compared to controls, significant decreases were found in these parameters except for MMP-9 in the treatment groups. While tissue MDA levels significantly increased in the DMBA group compared to the control group, SOD, CAT, GSH-Px activities and GSH levels significantly decreased. When the DMBA group and the treatment groups were compared, MDA levels significantly decreased only in the D+P+T while only the GSH levels of antioxidant parameters significantly increased in all treatment groups. While p53 and Bax expressions of apoptotic markers significantly decreased in the DMBA group compared to the control group, it was observed that Bcl-2 β-Catenin and cyclin D1 expressions significantly increased. It was observed that p53 and Bax expressions significantly increased in both D+P and D+P+T groups compared to the DMBA group, and these findings were supported by Tunnel and immunohistochemical findings. Cyclin D1 expressions were determined to significantly decrease only in the D+T group, which was supported by Tunnel and immunohistochemical findings. Immunohistochemical ER-α and Ki-67 immunoreactivities significantly increased in the DMBA group compared to the control group, but significant decreases were determined in all of the treatment groups. Our study results have shown that the combined administration of Pomegranate extract and Tangeretin may be more beneficial in preventing breast cancer development. Keywords: DMBA, Pomegranate Extract, Tangeretin, Breast Cancer, Chemopreventive