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HCMV-Mediated Interference of Bortezomib-Induced Apoptosis in Colon Carcinoma Cell Line Caco-2
Heike Härtel1, Janine Theiß1, Mohammed O Abdelaziz1
1Institute of Virology, Charité-Universitätsmedizin-Berlin, 10117 Berlin, Germany.
Abstract:
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.
Insights
Human cytomegalovirus (HCMV) infection protects colon cancer cells from apoptosis. Proteasome inhibitors may offer therapeutic potential for colon carcinoma, even in HCMV-infected cells.
Area of Science:
- Virology
- Oncology
- Cell Biology
Background:
- Human cytomegalovirus (HCMV) is linked to human malignancies, including colon cancer.
- Proteasome inhibitors are used in cancer therapy and affect HCMV infection.
Purpose of the Study:
- To investigate the therapeutic potential of proteasome inhibitors for colon carcinoma.
- To determine how HCMV infection influences this therapeutic potential.
Main Methods:
- Immunofluorescence and flow cytometry to assess Caco-2 cell susceptibility to HCMV.
- Growth curve analysis, protein expression kinetics, and quantitative genome analysis.
- Assessment of mitochondrial membrane potential and apoptosis inhibition in HCMV-infected cells under proteasome inhibitor treatment.
Main Results:
- Caco-2 colon carcinoma cells are susceptible to HCMV infection.
- HCMV exhibits an anti-apoptotic effect by inhibiting early apoptosis events and stabilizing mitochondrial membrane potential.
- This HCMV-induced stabilization is resistant to the proteasome inhibitor Bortezomib.
Conclusions:
- HCMV infection confers resistance to apoptosis in colon carcinoma cells.
- Proteasome inhibitors show potential in colon carcinoma therapy, with implications for HCMV-infected tumors.
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