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.
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.
Authors: Marilin S Koch; Mykola Zdioruk; Michal O Nowicki; Alec M Griffith; Estuardo Aguilar-Cordova; Laura K Aguilar; Brian W Guzik; Francesca Barone; Paul Peter Tak; Katharina Schregel; Michael S Hoetker; James A Lederer; E Antonio Chiocca; Ghazaleh Tabatabai; Sean E Lawler Journal: Mol Ther Oncolytics Date: 2022-07-31 Impact factor: 6.311