Oxidative stress enhances rotavirus oncolysis in breast cancer and leukemia, except in melanoma with abundant matrix

Objectives: This study aimed to explore the impact of oxidative stress and extracellular matrix integrity on rotavirus infection in various cancer cells, including breast cancer, acute lymphoblastic leukemia, and melanoma. Methods: We induced oxidative stress using ROS-inducing drugs (cisplatin, metronidazole, melatonin, valproic acid, doxorubicin, losartan, nitrofurantoin, and DHA) and investigated the effects on viral infection in MCF-7, Reh, A375, B16-F1, and SK-MEL-28 cells and the generation of virions from infected cells by harvesting the supernatants every two hours, reinfecting other cells, and analyzing cell viability and DNA fragmentation. Findings: In MCF-7 and Reh cells, rotavirus Wt1-5 infection led to increased ROS generation, virion production, membrane permeability, mitochondrial dysfunction, DNA damage, and cell death. These effects were amplified by ROS-inducing drugs. Conversely, melanoma cells (SK-MEL-28 and A375) with a robust extracellular matrix network showed limited sensitivity to the drugs. Notably, losartan, which modulates the extracellular matrix, enhanced viral infection in melanoma cells (99 %). Conclusions: Oxidative stress promotes oncolytic rotavirus infection in breast cancer and acute lymphoblastic leukemia cells, suggesting potential utility in combination with radiotherapy or chemotherapy due to their shared induction of intracellular oxidative stress.