Multidrug resistance (MDR) poses a significant problem in cancer treatment, often
causing adverse effects during chemotherapy. Ebselen (Ebs), a synthetic organoselenium
compound, affects cellular redox status in cancer cells. In the study, we observed
that Ebs disrupted cellular redox balance and sensitized drug‐resistant cells to doxorubicin
(DOX) treatment. The combination of Ebs and DOX led to increased intracellular reactive
oxygen species (ROS) levels and lipid peroxidation while decreasing the activity of
thioredoxin reductase (TrxR) and cellular antioxidants in drug‐resistant cells. Furthermore,
this combination treatment demonstrated notable chemosensitizing effects by reducing
cell viability and proliferation in MDR cells compared to DOX treatment alone. Additionally,
the combination of Ebs and DOX induced DNA fragmentation and exhibited G2/M phase
cell cycle arrest. Immunofluorescent analysis revealed that the Ebs and DOX combination
upregulated the expression of p53 and p21, which activated the mitochondrial‐dependent
apoptotic pathway. The combination treatment also enhanced the upregulation of proapoptotic
markers such as Bax, Caspase‐3, ‐9, and cytochrome C, while downregulating the expression
of the antiapoptotic marker Bcl‐2. Therefore, the current discoveries suggest that
Ebs could be employed as a drug candidate for reversing MDR in cancer cells by regulating
cellular redox homeostasis.
