HCMV-Mediated Interference of Bortezomib-Induced Apoptosis in Colon Carcinoma Cell Line Caco-2.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Bortezomib
/ pharmacology
Caco-2 Cells
Cell Death
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cells, Cultured
Cytomegalovirus
/ physiology
Cytomegalovirus Infections
/ metabolism
Fluorescent Antibody Technique
Genome, Human
Host-Pathogen Interactions
/ drug effects
Humans
Membrane Potential, Mitochondrial
Proteasome Inhibitors
/ pharmacology
Bortezomib
Caco-2 cells
apoptosis
co-culture
human cytomegalovirus
necroptosis
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
09 Jan 2021
09 Jan 2021
Historique:
received:
17
12
2020
revised:
04
01
2021
accepted:
06
01
2021
entrez:
13
1
2021
pubmed:
14
1
2021
medline:
2
3
2021
Statut:
epublish
Résumé
Human cytomegalovirus (HCMV) has been implicated in the development of human malignancies, for instance in colon cancer. Proteasome inhibitors were developed for cancer therapy and have also been shown to influence HCMV infection. The aim of this study was to investigate if proteasome inhibitors have therapeutic potential for colon carcinoma and how this is influenced by HCMV infection. We show by immunofluorescence and flow cytometry that the colon carcinoma cell line Caco-2 is susceptible to HCMV infection. Growth curve analysis as well as protein expression kinetics and quantitative genome analysis further confirm these results. HCMV has an anti-apoptotic effect on Caco-2 cells by inhibiting very early events of the apoptosis cascade. Further investigations showed that HCMV stabilizes the membrane potential of the mitochondria, which is typically lost very early during apoptosis. This stabilization is resistant to proteasome inhibitor Bortezomib treatment, allowing HCMV-infected cells to survive apoptotic signals. Our findings indicate a possible role of proteasome inhibitors in colon carcinoma therapy.
Identifiants
pubmed: 33435377
pii: v13010083
doi: 10.3390/v13010083
pmc: PMC7827311
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Proteasome Inhibitors
0
Bortezomib
69G8BD63PP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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