Abstract:
The disadvantages and side effects of currently available breast cancer (BC) therapies
have compelled researchers to seek new therapeutic strategies. This study was designed to
investigate the effect of selenium nanoparticles biosynthesized with carvacrol (SeNPs-CV) on
breast cancer (MCF-7) cell lines and to explore possible underlying pathways. Flow cytometry,
MTT assays, and various biochemical techniques were used to evaluate the anti-proliferative effects
of SeNPs-CV on MCF-7 cells. Cytotoxicity assays showed that treatment with SeNPs-CV could
effectively reduce MCF-7 cell proliferation and viability in a dose-dependent manner. However,
SeNPs-CV had no cytotoxic effect against Vero cells. Furthermore, SeNPs-CV showed better
anticancer activity than metal nanoparticles of selenium evidenced by the lower IC50 obtained
in MCF-7 cells (8.3 µg/mL versus 41.6 µg/mL, respectively). Treatment with SeNPs-CV directly
targeted Bcl-2, Bax, and caspase-3, leading to the mitochondrial leakage of cytochrome C and
subsequent activation of the apoptotic cascade in MCF-7 cells. In addition, MCF-7 cells treated
with SeNPs-CV exhibited elevated levels of oxidative stress, as indicated by noticeable rises in
8-OHDG, ROS, NO, and LPO, paralleled by significant exhaustion in GSH levels and antioxidant
enzymes activity. In addition, the administration of SeNPs-CV induced the inflammatory mediator
IL-1β and downregulated the expression of cell-proliferating nuclear antigen (PCNA) in MCF-7
cells, which plays a critical role in apoptosis. Therefore, the ability of SeNPs-CV to fight BC may
be due to its ability to induce oxidative stress, inflammation, and apoptosis in tumor cells. These
findings demonstrate the therapeutic potential of Se nanoparticles conjugated with CV, which may
provide a novel approach for combination chemotherapy in BC.
