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Transforming growth factor beta 1 induces apoptotic cell death in cultured human gastric carcinoma cells
1Department of Pathology, Hiroshima University, Japan.
Abstract:
Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor for many cell types, including tumor cells. We recently have reported the establishment and characterization of two human gastric scirrhous carcinoma cell lines, HSC-39 and HSC-43. Here we examined the effect of TGF-beta 1 on the growth of these lines as compared to five other human gastric adenocarcinoma cell lines. Proliferation of HSC-39 and HSC-43 cells was strongly inhibited by TGF-beta 1, whereas the other gastric adenocarcinoma cell lines were unresponsive to TGF-beta 1. Both HSC-39 and HSC-43 cells gradually lost viability following exposure to TGF-beta 1. This response was dose dependent up to 4 ng/ml. When TGF-beta 1 was removed, the cells failed to exhibit regrowth, indicating an irreversible growth-inhibitory effect of this agent, leading to cell death. DNA fragments were observed consisting of multimers of approximately 180 base pairs 24 h after TGF-beta 1 treatment. The chromatin condensation of each cell line was confirmed by Hoechst 33258 fluorochrome staining. Ultrastructurally, condensed and fragmented nuclei were observed in TGF-beta 1-treated cells. These features are generally associated with apoptotic processes. Both cell death and DNA fragmentation were partially inhibited by cycloheximide, suggesting the requirement for new protein synthesis. Our results suggest that TGF-beta 1 induces cell death in human gastric scirrhous carcinoma cells in vitro which is mediated by activation of a signal transduction pathway for apoptosis.
Insights
Transforming growth factor beta 1 (TGF-beta 1) inhibits growth and induces irreversible cell death in specific human gastric scirrhous carcinoma cells. This process involves apoptosis, requiring new protein synthesis for its full effect.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor beta 1 (TGF-beta 1) is a known growth inhibitor for various cell types, including tumor cells.
- Two human gastric scirrhous carcinoma cell lines, HSC-39 and HSC-43, were previously established and characterized.
Purpose of the Study:
- To investigate the effect of TGF-beta 1 on the proliferation and viability of HSC-39 and HSC-43 cells.
- To compare the response of these scirrhous carcinoma cell lines to TGF-beta 1 with five other human gastric adenocarcinoma cell lines.
Main Methods:
- Treatment of gastric carcinoma cell lines with varying concentrations of TGF-beta 1.
- Assessment of cell proliferation, viability, DNA fragmentation, and chromatin condensation.
- Ultrastructural analysis of cell nuclei.
- Evaluation of cycloheximide's effect on TGF-beta 1-induced cell death and DNA fragmentation.
Main Results:
- TGF-beta 1 strongly inhibited proliferation and induced irreversible cell death in HSC-39 and HSC-43 cells in a dose-dependent manner (up to 4 ng/ml).
- Other gastric adenocarcinoma cell lines tested were unresponsive to TGF-beta 1.
- TGF-beta 1 treatment led to DNA fragmentation and chromatin condensation, indicative of apoptosis.
- Cell death and DNA fragmentation were partially inhibited by cycloheximide, suggesting a requirement for new protein synthesis.
Conclusions:
- TGF-beta 1 effectively induces apoptosis and cell death in human gastric scirrhous carcinoma cells (HSC-39 and HSC-43) in vitro.
- The apoptotic process appears to be mediated by the activation of a specific signal transduction pathway.
- The differential response to TGF-beta 1 highlights potential therapeutic targets in gastric cancer treatment.
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