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    Investigation of the Proapoptotic Effects of Cetixumab and Selenium Combination on Laryngeal Cancer Cells via TRPM2 Channels
    (Dubai Iranian Hosp, 2025) Gunizi, Huseyin; Gunizi, Ozlem Ceren; Ovey, Shak Suat
    Background and Objectives: Cetuximab is commonly used as a chemotherapy drug for treating laryngeal cancer. Selenium, known for its antioxidant properties, is also believed to enhance the effectiveness of certain chemotherapeutic agents. This study aimed to evaluate how cetuximab and selenium influence the activation of the Transient Receptor Potential Melastatin 2 (TRPM2) channel. Methods: An observational study was conducted using cultured human laryngeal cancer cells (Hep-2). The cells were divided into seven experimental groups. Cumene hydroperoxide was used to stimulate the cells and activate TRPM2 channels, while antranilic acid was applied in certain groups to inhibit these channels. Measurements included cytosolic calcium levels, apoptosis, intracellular reactive oxygen species (ROS), mitochondrial depolarization, caspase-3 and caspase-9 activities, as well as immunohistochemical (IHC) staining. Statistical analysis was performed using GraphPad Prism 7.04, and data are presented as mean +/- standard deviation. Results: Compared to the cetuximab-only group, cells treated with both cetuximab and selenium showed significantly higher levels of apoptosis, intracellular calcium, ROS, and caspase-3 and caspase-9 activities (P<0.001). Inhibition of TRPM2 channels by antranilic acid significantly reduced apoptosis in these groups (P<0.05 and P<0.001). Conclusion: The pro-apoptotic effect of cetuximab on laryngeal cancer cells appears to be mediated through TRPM2 channels. Selenium enhances this apoptotic response by promoting TRPM2 channel activation and increasing calcium influx. These findings highlight selenium's regulatory role in apoptosis and calcium entry via TRPM2 channels.