Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus
AbstractStarvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects. View Full-Text
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Scheubeck, G.; Berchtold, S.; Smirnow, I.; Schenk, A.; Beil, J.; Lauer, U.M. Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus. Viruses 2019, 11, 614.
Scheubeck G, Berchtold S, Smirnow I, Schenk A, Beil J, Lauer UM. Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus. Viruses. 2019; 11(7):614.Chicago/Turabian Style
Scheubeck, Gabriel; Berchtold, Susanne; Smirnow, Irina; Schenk, Andrea; Beil, Julia; Lauer, Ulrich M. 2019. "Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus." Viruses 11, no. 7: 614.
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