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Solasodine Downregulates ABCB1 Overexpression in Multidrug Resistant Cancer Cells Via Inhibiting Nrf2/Keap1 Signaling
Pradhapsingh Bharathiraja1, Sugumar Baskar1, N Rajendra Prasad1
1Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India.
Journal of Cellular Biochemistry
|November 13, 2024
Summary
Solasodine combats multidrug-resistant cancer by disrupting redox balance and downregulating P-glycoprotein (P-gp) via the Nrf2/Keap1 pathway, enhancing chemotherapy effectiveness.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Multidrug-resistant (MDR) cancer cells evade apoptosis by maintaining redox homeostasis.
- P-glycoprotein (P-gp) overexpression is a key mechanism of MDR, contributing to chemotherapeutic failure.
Purpose of the Study:
- To investigate solasodine's effect on P-gp expression and its potential to sensitize drug-resistant cancer cells to chemotherapy.
- To elucidate the role of the Nrf2/Keap1 signaling pathway in solasodine-mediated chemosensitization.
Main Methods:
- Measurement of oxidative stress indicators (ROS, 8-OHdG, γ-H2AX) in drug-resistant KBChR-8-5 cells.
- Western blot and immunofluorescence analysis of Nrf2, Keap1, and P-gp (ABCB1) expression following solasodine treatment.
- Assessment of antioxidant enzyme activities (SOD, CAT, GPx) and glutathione (GSH) levels.
Main Results:
- Solasodine combined with doxorubicin increased intracellular ROS, DNA damage (8-OHdG, γ-H2AX), and lipid peroxidation.
- Solasodine inhibited Nrf2 nuclear translocation and ABCB1 gene activation, reducing P-gp overexpression.
- Combination therapy decreased antioxidant enzyme activities and GSH levels, disrupting redox balance.
Conclusions:
- Solasodine effectively overcomes MDR by downregulating P-gp expression through the Nrf2/Keap1 pathway.
- Solasodine disrupts the redox homeostasis in MDR cancer cells, making them more susceptible to chemotherapeutics.
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