TY - JOUR AU - Baskar, Sugumar AU - Bharathiraja, Pradhapsingh AU - Rajendra Prasad, N. TI - Sensitization of Multidrug Resistant Cancer Cells to Doxorubicin Using Ebselen by Disturbing Cellular Redox Status JF - CELL BIOCHEMISTRY AND FUNCTION J2 - CELL BIOCHEM FUNCT VL - 42 PY - 2024 IS - 7 SN - 0263-6484 DO - 10.1002/cbf.4134 UR - https://m2.mtmt.hu/api/publication/35481375 ID - 35481375 AB - 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. LA - English DB - MTMT ER - TY - CHAP AU - Mehraj, Safiya AU - Jan, Shariqa AU - Fatima, Kaneez AU - Shafi, Adil AU - Khan, Sameer Ullah ED - Khan, Sameer Ullah ED - Malik, Fayaz TI - Intracellular Compartments and Drug Resistance T2 - Drug Resistance in Cancer: Mechanisms and Strategies PB - Springer Nature Singapore CY - Singapore SN - 9789819716661 PY - 2024 SP - 269 EP - 295 PG - 27 DO - 10.1007/978-981-97-1666-1_9 UR - https://m2.mtmt.hu/api/publication/34842264 ID - 34842264 N1 - Chapter 9 LA - English DB - MTMT ER -