Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus

Starvation 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 protect...

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Bibliographic Details
Published in:Viruses 2019-07, Vol.11 (7), p.614
Main Authors: Scheubeck, Gabriel, Berchtold, Susanne, Smirnow, Irina, Schenk, Andrea, Beil, Julia, Lauer, Ulrich M
Format: Article
Language:English
Subjects:
Brain cancer
Breast cancer
Cancer therapies
Cell culture
Cell viability
Chemotherapy
Clinical trials
Colorectal cancer
Colorectal carcinoma
fasting
Glucose
Growth curves
Immunization
Immunotherapy
Infections
Insulin-like growth factors
Laboratories
Lysis
Measles
measles vaccine virus
Metastasis
Oncolysis
Patients
Quality of life
starvation
Tumor cell lines
Tumor cells
Tumors
Vaccines
virotherapy
Viruses
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Summary:Starvation 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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v11070614