Chemopreventive Potential of Brucine-Gold Nanoparticles (BRU-AuNPs) in DMBA-induced Mammary Cancer via Modulation of PI3K/AKT/mTOR Pathway.

This study investigates the effects of brucine-gold nanoparticles (BRU-AuNPs) on rat mammary carcinogenesis by analysing biochemical, histological, and molecular interactions. Mammary cancer was induced in female Sprague-Dawley rats via subcutaneous injection of a chemical carcinogen (DMBA 25 mg/rat) near the mammary gland. Different concentrations of BRU-AuNPs (0.25, 0.5, and 1 mg/kg b.w) were orally administered for 112 days to assess the optimum dose. Parameters including body weight changes, tumor incidence, tumor volume, and tumor burden were analysed in control and experimental rats. Biochemical analyses include lipid peroxidation, antioxidant status, detoxification enzyme activities, and lipid profiles. Histopathological examinations of mammary tissues were performed to evaluate tissue and cellular integrity. The results revealed that BRU-AuNPs treatment to DMBA-injected rats significantly reduced incidence, tumor weight, and burden, lipid peroxidation, and phase I detoxification enzyme activities. Conversely, it improved body weight, phase II detoxification enzyme activities, and antioxidant status compared to DMBA-alone injected rats. Histopathological findings confirmed the protective effect of BRU-AuNPs against DMBA-induced tissue damage. Furthermore, molecular studies demonstrated that BRU-AuNPs modulate the PI3K/AKT/mTOR pathway by downregulating p-PI3K, p-AKT, and p-mTOR gene expression while upregulating PTEN and PKD1 levels. These molecular alterations were validated through immunohistochemistry and Western blot analyses. In conclusion, BRU-AuNPs exhibit significant anticancer effects by modulating oxidative stress and inhibiting the PI3K/AKT/mTOR pathway. These findings highlight their potential as a promising therapeutic strategy for breast cancer prevention.