Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation.
<h4>Background</h4>Although radiotherapy is one of the mainstream approaches for the treatment of head and neck squamous cell carcinoma (HNSCC), this cancer is always associated with resistance to radiation. In this study, the mechanism of action of isoalantolactone as well as its radios...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0145790 |
| _version_ | 1819038256441851904 |
|---|---|
| author | Yonggang Fan Zhiyong Weng Hongguo Gao Jiehua Hu Hongyan Wang Lihua Li Hua Liu |
| author_facet | Yonggang Fan Zhiyong Weng Hongguo Gao Jiehua Hu Hongyan Wang Lihua Li Hua Liu |
| author_sort | Yonggang Fan |
| collection | DOAJ |
| description | <h4>Background</h4>Although radiotherapy is one of the mainstream approaches for the treatment of head and neck squamous cell carcinoma (HNSCC), this cancer is always associated with resistance to radiation. In this study, the mechanism of action of isoalantolactone as well as its radiosensitizing effect was investigated in UMSCC-10A cells.<h4>Methods</h4>The radiosensitization of UMSCC-10A cells treated with isoalantolactone was analyzed by colony formation assay. The radiosensitization effects of isoalantolactone on cell proliferation, cell cycle and apoptosis regulation were examined by BrdU incorporation assay, DNA content assay and flow cytometry, respectively. Western blotting was performed to determine the effects of isoalantolactone combined with radiation on the protein expression of Mek, extracellular signal-regulated kinase (Erk1/2) as well as phosphorylated Mek and Erk1/2. Erk1/2 knockdown by siRNA was used to confirm that isoalantolactone specifically inhibited the activation of Erk1/2 signaling pathway in UMSCC-10A cells.<h4>Results</h4>Isoalantolactone enhanced the radiosensitivity of UMSCC-10A cells; the sensitivity enhanced ratios (SERs) were 1.44 and 1.63, respectively, for 2.5 and 5 μM. Moreover, isoalantolactone enhanced radiation-induced cell proliferation and apoptosis and cell cycle arrested at G2/M phase. Furthermore, no marked changes were observed in the expression of total Erk1/2 and Mek protein after radiation treatment. However, isoalantolactone was significantly reduced radiation-induced the phosphorylation of Erk1/2, whereas it altered the phosphorylation of Mek to a lesser extent. In addition, the radiosensitivity of UMSCC-10A cells with Erk1/2 knockdown was increased. Isoalantolactone cannot further prevent the proliferation of UMSCC-10A cells with Erk1/2 knockdown which other mechanism regulated cell proliferation.<h4>Conclusion</h4>Our results suggested that isoalantolactone enhanced radiation-induced apoptosis, cell cycle arrested and reduced the cell proliferation of UMSCC-10A cells via specifically inhibited the phosphorylation of Erk1/2. Thus a low concentration of isoalantolactone may be used to overcome the resistance of UMSCC-10A cells to radiation and may be a promising radiosensitizer in cancer therapy. |
| first_indexed | 2024-12-21T08:34:25Z |
| format | Article |
| id | doaj.art-acd243bdf86b47a38f8366f9a9fb8485 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:34:25Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-acd243bdf86b47a38f8366f9a9fb84852022-12-21T19:10:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014579010.1371/journal.pone.0145790Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation.Yonggang FanZhiyong WengHongguo GaoJiehua HuHongyan WangLihua LiHua Liu<h4>Background</h4>Although radiotherapy is one of the mainstream approaches for the treatment of head and neck squamous cell carcinoma (HNSCC), this cancer is always associated with resistance to radiation. In this study, the mechanism of action of isoalantolactone as well as its radiosensitizing effect was investigated in UMSCC-10A cells.<h4>Methods</h4>The radiosensitization of UMSCC-10A cells treated with isoalantolactone was analyzed by colony formation assay. The radiosensitization effects of isoalantolactone on cell proliferation, cell cycle and apoptosis regulation were examined by BrdU incorporation assay, DNA content assay and flow cytometry, respectively. Western blotting was performed to determine the effects of isoalantolactone combined with radiation on the protein expression of Mek, extracellular signal-regulated kinase (Erk1/2) as well as phosphorylated Mek and Erk1/2. Erk1/2 knockdown by siRNA was used to confirm that isoalantolactone specifically inhibited the activation of Erk1/2 signaling pathway in UMSCC-10A cells.<h4>Results</h4>Isoalantolactone enhanced the radiosensitivity of UMSCC-10A cells; the sensitivity enhanced ratios (SERs) were 1.44 and 1.63, respectively, for 2.5 and 5 μM. Moreover, isoalantolactone enhanced radiation-induced cell proliferation and apoptosis and cell cycle arrested at G2/M phase. Furthermore, no marked changes were observed in the expression of total Erk1/2 and Mek protein after radiation treatment. However, isoalantolactone was significantly reduced radiation-induced the phosphorylation of Erk1/2, whereas it altered the phosphorylation of Mek to a lesser extent. In addition, the radiosensitivity of UMSCC-10A cells with Erk1/2 knockdown was increased. Isoalantolactone cannot further prevent the proliferation of UMSCC-10A cells with Erk1/2 knockdown which other mechanism regulated cell proliferation.<h4>Conclusion</h4>Our results suggested that isoalantolactone enhanced radiation-induced apoptosis, cell cycle arrested and reduced the cell proliferation of UMSCC-10A cells via specifically inhibited the phosphorylation of Erk1/2. Thus a low concentration of isoalantolactone may be used to overcome the resistance of UMSCC-10A cells to radiation and may be a promising radiosensitizer in cancer therapy.https://doi.org/10.1371/journal.pone.0145790 |
| spellingShingle | Yonggang Fan Zhiyong Weng Hongguo Gao Jiehua Hu Hongyan Wang Lihua Li Hua Liu Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. PLoS ONE |
| title | Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. |
| title_full | Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. |
| title_fullStr | Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. |
| title_full_unstemmed | Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. |
| title_short | Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. |
| title_sort | isoalantolactone enhances the radiosensitivity of umscc 10a cells via specific inhibition of erk1 2 phosphorylation |
| url | https://doi.org/10.1371/journal.pone.0145790 |
| work_keys_str_mv | AT yonggangfan isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation AT zhiyongweng isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation AT hongguogao isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation AT jiehuahu isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation AT hongyanwang isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation AT lihuali isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation AT hualiu isoalantolactoneenhancestheradiosensitivityofumscc10acellsviaspecificinhibitionoferk12phosphorylation |