Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus.


Journal

Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722

Informations de publication

Date de publication:
05 07 2019
Historique:
received: 23 05 2019
revised: 27 06 2019
accepted: 01 07 2019
entrez: 10 7 2019
pubmed: 10 7 2019
medline: 1 8 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31284426
pii: v11070614
doi: 10.3390/v11070614
pmc: PMC6669668
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Culture Media 0
Measles Vaccine 0

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Gabriel Scheubeck (G)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.

Susanne Berchtold (S)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.

Irina Smirnow (I)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.

Andrea Schenk (A)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.

Julia Beil (J)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.
German Cancer Consortium (DKTK), DKFZ Partner Site Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.

Ulrich M Lauer (UM)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany. ulrich.lauer@uni-tuebingen.de.
German Cancer Consortium (DKTK), DKFZ Partner Site Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany. ulrich.lauer@uni-tuebingen.de.

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