HCMV-Mediated Interference of Bortezomib-Induced Apoptosis in Colon Carcinoma Cell Line Caco-2.
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.
['Härtel|Heike|H|', 'Theiß|Janine|J|', 'Abdelaziz|Mohammed O|MO|', 'Raftery|Martin J|MJ|', 'Pecher|Gabriele|G|', 'Bogner|Elke|E|0000-0001-7622-2900']
D000970:Antineoplastic Agents D017209:Apoptosis D000069286:Bortezomib D018938:Caco-2 Cells D016923:Cell Death D045744:Cell Line, Tumor D049109:Cell Proliferation D002478:Cells, Cultured D003587:Cytomegalovirus D003586:Cytomegalovirus Infections D005455:Fluorescent Antibody Technique D015894:Genome, Human D054884:Host-Pathogen Interactions D006801:Humans D053078:Membrane Potential, Mitochondrial D061988:Proteasome Inhibitors
apoptosis human cytomegalovirus Caco-2 cells Bortezomib co-culture necroptosis