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Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells
Juan Cen1, Li Zhang1, Fangfang Liu1
1Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
Abstract:
Reactive oxygen species (ROS) play an important role in multidrug resistance (MDR). This study aimed to investigate the effects of long-term ROS alteration on MDR in MCF-7 cells and to explore its underlying mechanism. Our study showed both long-term treatments of H2O2 and glutathione (GSH) led to MDR with suppressed iROS levels in MCF-7 cells. Moreover, the MDR cells induced by 0.1 μM H2O2 treatment for 20 weeks (MCF-7/ROS cells) had a higher viability and proliferative ability than the control MCF-7 cells. MCF-7/ROS cells also showed higher activity or content of intracellular antioxidants like glutathione peroxidase (GPx), GSH, superoxide dismutase (SOD), and catalase (CAT). Importantly, MCF-7/ROS cells were characterized by overexpression of MDR-related protein 1 (MRP1) and P-glycoprotein (P-gp), as well as their regulators NF-E2-related factor 2 (Nrf2), hypoxia-inducible factor 1 (HIF-1α), and the activation of PI3K/Akt pathway in upstream. Moreover, several typical MDR mediators, including glutathione S-transferase-π (GST-π) and c-Myc and Protein Kinase Cα (PKCα), were also found to be upregulated in MCF-7/ROS cells. Collectively, our results suggest that ROS may be critical in the generation of MDR, which may provide new insights into understanding of mechanisms of MDR.
Insights
Long-term reactive oxygen species (ROS) alteration induced multidrug resistance (MDR) in MCF-7 cells. This study reveals ROS
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- Reactive oxygen species (ROS) are implicated in the development of multidrug resistance (MDR).
- Understanding the role of ROS in MDR is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the impact of long-term reactive oxygen species (ROS) alteration on multidrug resistance (MDR) in MCF-7 cells.
- To elucidate the underlying molecular mechanisms by which ROS influences MDR.
Main Methods:
- Long-term treatment of MCF-7 cells with hydrogen peroxide (H2O2) and glutathione (GSH).
- Assessment of cell viability, proliferation, and intracellular antioxidant levels (GPx, GSH, SOD, CAT).
- Analysis of the expression and activity of MDR-related proteins (MRP1, P-gp) and their regulators (Nrf2, HIF-1α, PI3K/Akt pathway, GST-π, c-Myc, PKCα).
Main Results:
- Long-term H2O2 and GSH treatments induced MDR in MCF-7 cells, accompanied by suppressed intracellular ROS (iROS) levels.
- MCF-7/ROS cells exhibited enhanced viability, proliferation, and elevated levels of intracellular antioxidants.
- MCF-7/ROS cells overexpressed MDR proteins (MRP1, P-gp) and their regulators (Nrf2, HIF-1α), with activated PI3K/Akt pathway. Upregulation of GST-π, c-Myc, and PKCα was also observed.
Conclusions:
- Long-term ROS modulation is critical in the generation of multidrug resistance (MDR) in MCF-7 cells.
- The study provides novel insights into the intricate mechanisms linking ROS and MDR, potentially guiding future therapeutic strategies.
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