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Updated: Jun 11, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Sensitization of Multidrug Resistant Cancer Cells to Doxorubicin Using Ebselen by Disturbing Cellular Redox Status
Sugumar Baskar1, Pradhapsingh Bharathiraja1, N Rajendra Prasad1
1Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamilnadu, India.
Abstract:
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.
Insights
Ebselen reverses multidrug resistance in cancer by disrupting redox balance and sensitizing cells to doxorubicin. This combination therapy enhances apoptosis and reduces cancer cell viability.
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.
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