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Regulation of transforming growth factor-beta 1-mediated apoptosis in head and neck squamous cell carcinoma
D C Duffey1, T C Calcaterra, A K Lichtenstein
1Division of Head and Neck Surgery, University of California at Los Angeles School of Medicine, 90024-1624, USA.
Abstract:
The apoptotic cell death in Cal-27 cells induced by exposure to transforming growth factor-beta 1 was inhibited by the endonuclease inhibitor aurintricarboxylic acid (ATA) in a concentration-dependent fashion. In vitro studies of cytotoxicity, DNA fragmentation, and protein synthesis by Cal-27 cell lines were performed. Inhibition of cytotoxicity as well as endonucleolytic DNA cleavage was detected. ATA did not inhibit cytotoxicity either via transforming growth factor cell-surface-receptor alteration or by inhibition of macromolecular synthesis. ATA-sensitive events occurred late during treatment. These data suggest that endonucleolytic DNA cleavage is a mandatory event leading to cell death in this system.
Insights
Aurintricarboxylic acid (ATA) inhibits transforming growth factor-beta 1-induced cell death in Cal-27 cells. This suggests that DNA fragmentation is essential for this specific apoptotic pathway.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Transforming growth factor-beta 1 (TGF-β1) is a key regulator of cellular processes, including apoptosis.
- Cal-27 cells are a human oral cancer cell line susceptible to TGF-β1-induced apoptosis.
Purpose of the Study:
- To investigate the role of endonuclease activity in TGF-β1-induced apoptosis of Cal-27 cells.
- To determine the mechanism by which aurintricarboxylic acid (ATA) inhibits this apoptotic process.
Main Methods:
- In vitro studies involving Cal-27 cell lines.
- Assessment of cytotoxicity, DNA fragmentation, and protein synthesis.
- Evaluation of ATA's effects at varying concentrations.
Main Results:
- ATA inhibited TGF-β1-induced apoptosis in a concentration-dependent manner.
- ATA suppressed both cytotoxicity and endonucleolytic DNA cleavage.
- Inhibition was not mediated by alterations in TGF-β1 cell-surface receptors or macromolecular synthesis.
Conclusions:
- Endonucleolytic DNA cleavage is a critical, mandatory event in TGF-β1-induced apoptosis of Cal-27 cells.
- ATA acts as an effective inhibitor of this specific apoptotic pathway by targeting DNA fragmentation.