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Inhibition of head and neck squamous cell carcinoma cell lines by transforming growth factor-beta
K B Briskin1, C Fady, R A Mickel
1Division of Head and Neck Surgery, University of California, Los Angeles School of Medicine, USA.
Abstract:
Transforming growth factor-beta is known to be a potent autocrine growth inhibitor produced by a wide variety of cells, including cells of the immune system. Other investigators have noted that the growth of nontransformed keratinocytes is inhibited by transforming growth factor-beta, whereas various carcinoma cell lines are resistant to these effects. Head and neck squamous cell carcinoma cells are known to have surface receptors for this cytokine. We thus assessed the effect of transforming growth factor-beta on the growth of head and neck squamous cell carcinoma cell lines. Four head and neck squamous cell carcinoma cell lines were incubated with varying concentrations of transforming growth factor-beta, and cytotoxicity was evaluated with a methylene blue colorimetric assay. After culturing in transforming growth factor-beta for 4 days, inhibition of growth was detected in CAL-27 (maximal inhibition at 5.0 ng/ml), UMSCC-1, and UMSCC-19 (maximal inhibition at 50 ng/ml) cell lines. One other cell line, UMSCC-8 was found resistant to the inhibitory effects of transforming growth factor-beta. Kinetics analysis experiments revealed minimal inhibition before day 2 of incubation, at which time inhibition increased linearly to day 4. Assessment of double-stranded DNA fragmentation suggested that DNA fragmentation occurs before significant cytotoxicity. Electron microscopic analysis and gel electrophoresis of extracted DNA revealed morphologic features consistent with apoptotic cell death. Our findings indicate that transforming growth factor-beta significantly inhibits the growth of head and neck squamous cell carcinoma cell lines by inducing apoptotic cell death.
Insights
Transforming growth factor-beta inhibits head and neck squamous cell carcinoma growth by inducing apoptosis. This cytokine shows potent anti-cancer effects in specific cell lines, offering potential therapeutic insights.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Transforming growth factor-beta (TGF-β) is a known autocrine inhibitor of normal cell growth, including immune cells.
- While TGF-β inhibits nontransformed keratinocytes, many carcinoma cell lines exhibit resistance.
- Head and neck squamous cell carcinoma (HNSCC) cells possess surface receptors for TGF-β.
Purpose of the Study:
- To investigate the effect of TGF-β on the growth of HNSCC cell lines.
- To determine the mechanism by which TGF-β influences HNSCC proliferation.
Main Methods:
- Four HNSCC cell lines were treated with varying concentrations of TGF-β.
- Cytotoxicity was assessed using a methylene blue colorimetric assay.
- DNA fragmentation, electron microscopy, and gel electrophoresis were used to evaluate cell death mechanisms.
Main Results:
- TGF-β significantly inhibited growth in CAL-27, UMSCC-1, and UMSCC-19 cell lines, with maximal effects at 5.0-50 ng/ml.
- UMSCC-8 cell line demonstrated resistance to TGF-β's inhibitory effects.
- Inhibition increased linearly from day 2 to day 4, and DNA fragmentation preceded significant cytotoxicity, indicating apoptosis.
Conclusions:
- TGF-β effectively inhibits the growth of specific HNSCC cell lines.
- The mechanism of growth inhibition involves the induction of apoptotic cell death.
- These findings suggest TGF-β as a potential therapeutic agent for HNSCC.