Modulatory effects of bisdemethoxycurcumin-conjugated silver/selenium nanoparticles on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis

Abstract Compared with curcumin, bisdemethoxycurcumin, a dimethoxy derivative of curcumin, is a bioactive compound with greater anti-inflammatory and anticancer effects. However, its hydrophobic nature, rapid metabolism, and poor bioavailability have limited its application in cancer therapy. This study investigates the modulatory effects of bis-demethoxycurcumin-conjugated silver/selenium nanoparticles (BDMC-AgSeNPs) on 7,12-dimethylbenz(a)anthracene-induced tumorigenesis. BDMC-conjugated bimetallic spherical Ag templates decorated with Se nanodots were fabricated and characterized via solid-state techniques. The BDMC-AgSeNPs were employed as nanocarriers, and their anticancer efficacy was evaluated. The results revealed that the viability of MCF-7 cells decreased with increasing concentrations of BDMC, AgSeNPs, and BDMC-AgSeNPs, with IC 50 values of 22.41, 10.20, and 8.07, respectively. In vivo, BDMC-AgSeNPs significantly decreased lactate dehydrogenase activity by 52%. In the same manner, BDMC-AgSeNPs reduced the serum malondialdehyde level by 35%. Additionally, BDMC-AgSeNPs drastically increased mammary superoxide dismutase and glutathione peroxidase activities by 52% and 47%, respectively. In contrast, mammary nitric oxide and malondialdehyde levels decreased in BDMC-AgSeNPs-rats. Immunohistochemistry showed mild expression of progesterone and human epidermal receptors in BDMC-AgSeNPs-treated rats. In addition, BDMC-AgSeNPs and AgSeNPs reduced Bcl-2-associated X-protein (BAX) levels. Histological examination revealed mammary glands with moderate proliferating ducts and fibrosis in DMBA-rats, while post-treatment with BDMC-AgSeNPs appeared to reveal normal ductal epithelial cells with stromal hyalinization foci. Overall, post-treatment with BDMC-AgSeNPs enhanced antioxidant status and apoptosis, with decreased levels of inflammatory biomarkers. In conclusion, BDMC-AgSeNPs mitigate mammary tumorigenesis by targeting cellular inflammation and apoptotic pathways. Graphical Abstract