Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 69 79 Mohammad Ali Akbar Esfahani Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Ruhollah Dorostkar Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Hadi Esmaeili Gouvarchin Ghaleh Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Reihaneh Ramezani Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical sciences, Tehran, Iran. Reihaneh Ramezani Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Seyyed Mohsen Mir Mohammad Sadeghi Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Akbar Ghorbani Alvanegh Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Seyed Kiarash Aghayan Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 07 21 2025 09 16 TC-1 is a recognized cancer cell line derived from lung epithelial cells that have been altered using the oncogenic E6 and E7 genes of human papillomavirus (HPV). These TC-1 cells are frequently utilized in preclinical research focused on lung cancer and HPV-associated tumors. The incidence of lung cancer and HPV-related cancers is significantly increasing. Drug resistance and the lack of selectivity in current treatments reduce their effectiveness. Researchers are seeking new therapeutic methods, including targeted therapies, immunotherapy, and oncolytic virus and bacterial therapies, to improve treatment outcomes and decrease mortality associated with these diseases. In this context, the present original study aimed to evaluate the potency of wild-type Newcastle disease virus (NDV-WTS) on lactate dehydrogenase (LDH) secretion and the induction of apoptosis in TC-1 cells. In this experimental study, the TC-1 cell lines were cultured under laboratory conditions. Subsequently, they were treated with different multiplicities of infection (MOIs) of NDV-WTS (1, 2, and 4). Finally, the oncolytic effects of the virus were evaluated using laboratory assays, including MTT (cell viability), reactive oxygen species (ROS), LDH, survival rates, and the activities of Caspases 8 and 9. The results indicated that NDV-WTS significantly decreased cell viability while increasing apoptosis, ROS levels, LDH release, and Caspase 8 and 9 activities compared to the control group. Molecular analyses further revealed that treatment of TC-1 cells with NDV significantly increased the expression of Bax, Casp8, and Casp9, while significantly decreasing Bcl2 expression relative to the control group. NDV-WTS demonstrated remarkable efficacy in treating lung cancer and HPV-associated tumors. Based on the results of the present study, the use of Newcastle disease virus in the treatment of lung cancer and HPV-associated tumors may be beneficial, which requires further studies and clinical trials. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4528 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4528/2259