Pre-clinical Evaluation of Karanjin Against DMBA-Induced Breast Cancer in Female Sprague-Dawley Rats Through Modulation of SMAR1 and CDP/CUx genes.

Purpose: To investigate the chemoprotective potential of karanjin against 7,12-dimethylbenz(α)anthracene (DMBA)-induced breast cancer.

Methodology: Thirty-six female rats were utilized for the study. Breast cancer was induced through a subcutaneous injection of 35 mg/kg DMBA. The animals were allocated to six groups. Three groups were allocated for karanjin (50 mg/kg, 100 mg/kg, and 200 mg/kg), and received daily treatment for 20 weeks (including 2 weeks as pre-treatment). Doxorubicin (4 mg/kg) was administered to the standard control group twice a week for 20 weeks. The disease control (DC) and normal control (NC) groups received daily treatment with saline. After the treatment, oxidative stress parameters, biochemical parameters, and inflammatory parameters were estimated. CCAAT-displacement protein/cut homeobox (CUP/Cux) and scaffold/matrix attachment region binding protein 1 (SMAR1) expression levels were measured through gene expression analysis. Immunohistochemical (IHC) analysis was performed to estimate the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2).

Results: Tumor growth reduced significantly (P-value < 0.01) in karanjin-treated animals compared to the DC group. Karanjin significantly (P-value < 0.01) regulated the levels of oxidative stress parameters, biochemical parameters, and inflammatory parameters compared to the DC group. Karanjin treatment significantly (P-value < 0.001) regulated the expression levels of SMAR1 and CDP/Cux. A notable reduction in the IHC scores was observed for ER, PR, and HER2 expression in karanjin groups.

Conclusion: Karanjin demonstrated chemoprotective activity against DMBA-induced breast cancer in animals potentially through modulation of SMAR1 and CDP/Cux gene expression and reduction of ER, PR and HER2 expression levels.