Sensitization of Multidrug Resistant Cancer Cells to Doxorubicin Using Ebselen by Disturbing Cellular Redox Status

Area of Science:

• Oncology
• Biochemistry
• Pharmacology

Background:

• Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, leading to treatment failure and adverse effects.
• Ebselen (Ebs), a synthetic organoselenium compound, modulates cellular redox status and shows potential in cancer therapy.

Purpose of the Study:

• To investigate the potential of Ebselen in reversing multidrug resistance (MDR) in cancer cells.
• To elucidate the mechanisms by which Ebselen sensitizes drug-resistant cells to doxorubicin (DOX).

Main Methods:

• Drug-resistant cancer cells were treated with Ebselen and Doxorubicin (DOX) alone and in combination.
• Assessed intracellular reactive oxygen species (ROS) levels, lipid peroxidation, and antioxidant enzyme activity (thioredoxin reductase).
• Evaluated cell viability, proliferation, DNA fragmentation, cell cycle progression, and apoptosis-related protein expression (p53, p21, Bax, Bcl-2, Caspase-3, -9, cytochrome C).

Main Results:

• Ebselen disrupted cellular redox balance and sensitized MDR cells to DOX.
• The combination treatment increased ROS and lipid peroxidation, decreased thioredoxin reductase activity and antioxidant levels.
• Ebselen and DOX combination reduced cell viability and proliferation, induced DNA fragmentation, G2/M cell cycle arrest, and promoted apoptosis via the mitochondrial pathway.

Conclusions:

• Ebselen effectively reverses multidrug resistance in cancer cells by modulating cellular redox homeostasis.
• The combination of Ebselen and Doxorubicin offers a promising strategy for overcoming chemotherapy resistance.
• Ebselen demonstrates potential as a therapeutic agent for enhancing the efficacy of existing cancer treatments.