Assessing the oncolytic potential of rotavirus on mouse myeloma cell line Sp2/0-Ag14

Abstract

Introduction: Cancer is the second leading cause of death in the United States surpassed only by cardiovascular disease. However, cancer has now overtaken cardiovascular disease as the main cause of death in 12 countries located in Western Europe. The burden of cancer is posing a major challenge to health care systems worldwide and improvements in methods for cancer prevention, diagnosis and treatment are being demanded. Alternative and complementary strategies for orthodox surgery, radiotherapy and chemotherapy need to be developed. Objective: To determine the oncolytic potential of tumor cell-adapted rotavirus in terms of their ability to infect and lysate murine myeloma Sp2/0-Ag14 cells. Materials and methods: Rotaviruses Wt1-5, WMW, TRUYO, ECwt-O, and WTEW were inoculated in Sp2/0-Ag14 cells and their infectious effects examined by immunochemistry, immunofluorescence, flow cytometry, and DNA fragmentation assays. Results: Rotavirus infection involved the participation of some heat shock proteins, protein disulfide isomerase (PDI) and integrin β3. Accumulation of viral antigens within the virus-inoculated cells and in the culture medium was detected for all the rotavirus isolates used. The rotavirus-induced cell death mechanism in Sp2/0-Ag14 cells involved changes in cell membrane permeability, chromatin condensation, and DNA fragmentation, which were compatible with cytotoxicity and apoptosis. Conclusions: The ability of the rotavirus isolates Wt1-5, WMW, TRUYO, ECwt-O, and WTEW to infect and cause cell death of Sp2/0-Ag14 cells, through mechanisms that are compatible with virus-induced apoptosis, makes these rotaviruses potential candidates to be used as oncolytic agents.