The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of onco...

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Main Authors: Iris Maria Forte, Paola Indovina, Serena Montagnaro, Aurora Costa, Carmelina Antonella Iannuzzi, Francesca Capone, Rosa Camerlingo, Anna Maria Malfitano, Francesca Pentimalli, Gianmarco Ferrara, Massimiliamo Quintiliani, Giuseppe Portella, Antonio Giordano, Roberto Ciarcia
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/13/12/2458
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author Iris Maria Forte
Paola Indovina
Serena Montagnaro
Aurora Costa
Carmelina Antonella Iannuzzi
Francesca Capone
Rosa Camerlingo
Anna Maria Malfitano
Francesca Pentimalli
Gianmarco Ferrara
Massimiliamo Quintiliani
Giuseppe Portella
Antonio Giordano
Roberto Ciarcia
author_facet Iris Maria Forte
Paola Indovina
Serena Montagnaro
Aurora Costa
Carmelina Antonella Iannuzzi
Francesca Capone
Rosa Camerlingo
Anna Maria Malfitano
Francesca Pentimalli
Gianmarco Ferrara
Massimiliamo Quintiliani
Giuseppe Portella
Antonio Giordano
Roberto Ciarcia
author_sort Iris Maria Forte
collection DOAJ
description Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.
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spelling doaj.art-8f3394d13d974c7ca2da05c47c64a3d52023-11-23T10:58:13ZengMDPI AGViruses1999-49152021-12-011312245810.3390/v13122458The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy ApproachIris Maria Forte0Paola Indovina1Serena Montagnaro2Aurora Costa3Carmelina Antonella Iannuzzi4Francesca Capone5Rosa Camerlingo6Anna Maria Malfitano7Francesca Pentimalli8Gianmarco Ferrara9Massimiliamo Quintiliani10Giuseppe Portella11Antonio Giordano12Roberto Ciarcia13Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, 80131 Naples, ItalyInstitute for High Performance Computing and Networking, National Research Council of Italy (ICAR-CNR), 80131 Naples, ItalyDepartment of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, 80137 Naples, ItalyDepartment of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyCell Biology and Biotherapy Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, 80131 Naples, ItalyExperimental Pharmacology Unit—Laboratories of Naples and Mercogliano (AV), Istituto Nazionale per lo Studio e la Cura deiTumori “Fondazione G. Pascale”, 80131 Naples, ItalyCell Biology and Biotherapy Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, 80131 Naples, ItalyDipartimento Scienze Mediche Traslazionali, Università di Napoli “Federico II”, 80131 Naples, ItalyCell Biology and Biotherapy Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, 80131 Naples, ItalyDepartment of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, 80137 Naples, ItalyDepartment of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDipartimento Scienze Mediche Traslazionali, Università di Napoli “Federico II”, 80131 Naples, ItalySbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, 80137 Naples, ItalyMalignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.https://www.mdpi.com/1999-4915/13/12/2458malignant mesothelioma (MM)oncolytic virus (OV)caprine herpesvirus 1 (CpHV-1)cisplatinsynergismapoptosis
spellingShingle Iris Maria Forte
Paola Indovina
Serena Montagnaro
Aurora Costa
Carmelina Antonella Iannuzzi
Francesca Capone
Rosa Camerlingo
Anna Maria Malfitano
Francesca Pentimalli
Gianmarco Ferrara
Massimiliamo Quintiliani
Giuseppe Portella
Antonio Giordano
Roberto Ciarcia
The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach
Viruses
malignant mesothelioma (MM)
oncolytic virus (OV)
caprine herpesvirus 1 (CpHV-1)
cisplatin
synergism
apoptosis
title The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach
title_full The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach
title_fullStr The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach
title_full_unstemmed The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach
title_short The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach
title_sort oncolytic caprine herpesvirus 1 cphv 1 induces apoptosis and synergizes with cisplatin in mesothelioma cell lines a new potential virotherapy approach
topic malignant mesothelioma (MM)
oncolytic virus (OV)
caprine herpesvirus 1 (CpHV-1)
cisplatin
synergism
apoptosis
url https://www.mdpi.com/1999-4915/13/12/2458
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