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 in Western Europe. The burden of cancer is posing a major challenge to health care systems worldwide and demanding improvements in methods for cancer prevention, diagnosis, and treatment. 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: We inoculated rotaviruses Wt1-5, WWM, TRUYO, ECwt-O, and WTEW in Sp2/0-Ag14 cells and we examined their infectious effects by immunocytochemistry, immunofluorescence, flow cytometry, and DNA fragmentation assays.Results: Rotavirus infection involved the participation of some heat shock proteins, of protein disulfide isomerase (PDI), and integrin β3. We detected the accumulation of viral antigens within the virus-inoculated cells and in the culture medium in all the rotavirus isolates examined. 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, WWM, 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 them potential candidates as oncolytic agents.

Isolation, Propagation and Genotyping of Human Rotaviruses Circulating among Children with Gastroenteritis in Two Egyptian University Hospitals

“…In the present study, we successfully adapted five rotavirus isolates to grow and induce cell death in colonic (Caco-2) tumor cells, which represent one of the most epidemiologically important human cancers. This remarkable property of the isolated rotaviruses makes them promising candidates for use as oncolytic agents, in the future [ 49 ]. Phylogenetic analysis revealed that the VP6, VP4, and VP7 segments of RVA144 isolated from Egyptian clinical specimens belong to G1P[8].…”

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

“…Mostly, we focused on the promising combinations based on the published clinical data, rather than presenting all oncolytic virus variations. Nevertheless, many preclinical and clinical studies using vaccines (e.g., yellow fever 17D strain [ 231 ]), attenuated (Zika virus [ 232 ]) or cancer cell-adapted viruses (e.g., rotavirus [ 233 ]) are currently ongoing and demonstrating encouraging results [ 234 ]. Repurposing the virus vaccines for cancer immunotherapy is of particular interest since the pre-existing viral immunity may increase oncolytic effectiveness.…”

Preclinical evaluation of oncolytic potential human rotavirus Wt 1-5 in gastric adenocarcinoma

“…Moreover, from 12 hours post-infection, cells positive for viral antigens and negative for DAPI staining were observed, indicating the rupture and destruction of cellular DNA ( Fig 2A ). This mechanism of cell death, known as oncosis, has been associated with alterations in the transport and metabolism of calcium, leading to osmotic rupture, as previously reported in MA104 and Sp2 /0-Ag14 cancer cells [ 18 , 77 ].…”

“…These mechanisms are favored by conformational changes that depend on thiol-disulfide exchanges by protein disulfide isomerase (PDI). It has been shown that the infective capacity of RV is reduced by blocking its union with antibodies directed against these proteins [15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”