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The Role of TRPM2 Channel in Doxorubicin-induced Cell Damage in Laryngeal Squamous Cancer Cells
Tarık Yağcı1, Ramazan Çınar2, Halil İbrahim Altıner3
1Department of ENT, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik, Türkiye.
Abstract:
Laryngeal squamous cell carcinoma is a common type of head and neck cancer. This study investigated the role of the TRPM2 channel in doxorubicin (DOX)-induced cell damage in human laryngeal squamous cancer cells (Hep-2). Cells were exposed to various DOX concentrations and the appropriate dose was found. Then, TRPM2 antagonist ACA was treated. At the end of the study, cell viability test, Western blot and oxidative stress and inflammatory markers were examined. The results showed that TRPM2 channel expression increased with DOX administration, and DOX incubation in cells caused an increase in ROS, MDA, IL-1β, IL-6, and TNF-α levels, while GSH and GSH-Px levels decreased. Concurrent treatment with ACA attenuated these effects and reduced oxidative stress and inflammation. In addition, DOX-induced apoptosis markers including Casp-3, Casp-8, Casp-9, p53, and Bax were elevated, while Bcl-2 levels were decreased; ACA treatment reversed these changes. The study demonstrated that DOX treatment significantly enhances TRPM2 channel activation and ROS production in Hep-2 cells, thereby initiating apoptotic pathways that lead to cell death. Consequently, targeting the TRPM2 channel may represent a promising therapeutic strategy for treating laryngeal cancer.
Insights
This study reveals that the TRPM2 channel exacerbates doxorubicin-induced damage in laryngeal cancer cells by increasing oxidative stress and apoptosis. Targeting this channel may offer a new therapeutic approach for laryngeal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Laryngeal squamous cell carcinoma is a prevalent head and neck cancer.
- Doxorubicin (DOX) is a chemotherapy agent used in cancer treatment.
- The role of the TRPM2 channel in DOX-induced cellular damage in laryngeal cancer remains unclear.
Purpose of the Study:
- To investigate the involvement of the TRPM2 channel in doxorubicin (DOX)-induced damage in human laryngeal squamous cancer cells (Hep-2).
- To evaluate the potential of targeting the TRPM2 channel as a therapeutic strategy for laryngeal cancer.
Main Methods:
- Hep-2 cells were treated with varying concentrations of DOX to determine an effective dose.
- TRPM2 channel activity was modulated using a specific antagonist (ACA).
- Cell viability, Western blot analysis, and assessments of oxidative stress (ROS, MDA, GSH, GSH-Px) and inflammatory markers (IL-1β, IL-6, TNF-α) were performed.
- Apoptosis markers (Casp-3, -8, -9, p53, Bax, Bcl-2) were analyzed.
Main Results:
- DOX treatment increased TRPM2 channel expression, ROS, MDA, IL-1β, IL-6, and TNF-α levels, while decreasing GSH and GSH-Px levels.
- ACA treatment attenuated DOX-induced oxidative stress and inflammation.
- DOX elevated apoptosis markers (Casp-3, -8, -9, p53, Bax) and decreased Bcl-2; ACA reversed these effects.
- DOX enhanced TRPM2 channel activation and ROS production, initiating apoptosis in Hep-2 cells.
Conclusions:
- DOX-induced cell damage in laryngeal cancer is mediated through TRPM2 channel activation and subsequent oxidative stress and apoptosis.
- Inhibition of the TRPM2 channel can mitigate DOX-induced cellular damage, reduce oxidative stress, and suppress apoptosis.
- Targeting the TRPM2 channel presents a potential therapeutic strategy for laryngeal cancer treatment.
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