Related Experiment Video
Updated: May 27, 2026
Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
Published on: October 21, 2012
Mode of cell death associated with adenovirus-mediated suicide gene therapy in HNSCC tumor model
Deepika Srivastava1, Ganesh Joshi, Kumaravel Somasundaram
1ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
Background:
Adenoviral mediated suicide gene therapy has been shown to have a tumoricidal effect against a variety of tumor models. Although the efficacy of this treatment regimen has been verified, the molecular mechanism of Herpes simplex virus thymidine kinase gene (HSVtk)- and ganciclovir (GCV)-induced cell death is still not well established.
Materials And Methods:
The mode of cell death by adenoviral (Adv)-HSVtk/GCV was examined in the head and neck squamous cell carcinoma cell line, NT8e.
Results:
The cell death was independent of apoptotic gene expression. Moreover apoptosis was not evident from cell cycle kinetic analysis. Adv-HSVtk/GCV treated cells showed time dependent accumulation of cells in the S-phase of the cell cycle although there was no increase in the "apoptotic peak" or sub-G1 population. Swelling of the cytoplasm without apparent nuclear condensation suggested a possible involvement of necrosis.
Conclusion:
The apoptotic mechanism may not play a central role in the Adv-HSVtk/GCV induced NT8e cell death and other mechanisms should be considered.
Insights
Adenoviral-mediated suicide gene therapy using Herpes simplex virus thymidine kinase gene (HSVtk) and ganciclovir (GCV) does not primarily induce apoptosis in head and neck cancer cells. Further research is needed to understand the exact cell death mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Adenoviral-mediated suicide gene therapy demonstrates tumoricidal effects.
- The precise molecular mechanisms of Herpes simplex virus thymidine kinase gene (HSVtk) and ganciclovir (GCV) induced cell death remain unclear.
Purpose of the Study:
- To investigate the mode of cell death induced by adenoviral (Adv)-HSVtk/GCV treatment.
- To elucidate the molecular pathways involved in cancer cell death.
Main Methods:
- Utilized the head and neck squamous cell carcinoma cell line, NT8e.
- Examined cell death mechanisms through gene expression analysis and cell cycle kinetics.
Main Results:
- Cell death induced by Adv-HSVtk/GCV was independent of apoptotic gene expression.
- Adv-HSVtk/GCV treatment led to S-phase accumulation without an increase in the sub-G1 population.
- Cytoplasmic swelling suggested potential involvement of necrosis.
Conclusions:
- Apoptosis may not be the primary mechanism of cell death in Adv-HSVtk/GCV treated NT8e cells.
- Alternative cell death pathways should be explored for this gene therapy approach.
More Related Videos
05:45In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021