γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model
Angiogenesis is one of the key hallmarks of cancer. In this study, we investigated whether γ-tocotrienol can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and if so, through what molecular mechanisms. We observed that γ-tocotrienol inhibited vascular endothelial growt...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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Impact Journals LLC
2014
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| Online Access: | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1876 http://hdl.handle.net/20.500.11937/16896 |
| _version_ | 1848749307785641984 |
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| author | Siveen, K. Ahn, K. Ong, T. Shanmugam, M. Li, F. Yap, W. Kumar, Alan Prem Fong, C. Tergaonkar, V. Hui, K. Sethi, G. |
| author_facet | Siveen, K. Ahn, K. Ong, T. Shanmugam, M. Li, F. Yap, W. Kumar, Alan Prem Fong, C. Tergaonkar, V. Hui, K. Sethi, G. |
| author_sort | Siveen, K. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Angiogenesis is one of the key hallmarks of cancer. In this study, we investigated whether γ-tocotrienol can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and if so, through what molecular mechanisms. We observed that γ-tocotrienol inhibited vascular endothelial growth factor (VEGF)-induced migration, invasion, tube formation and viability of HUVECs in vitro. Moreover, γ-tocotrienol reduced the number of capillary sprouts from matrigel embedded rat thoracic aortic ring in a dose-dependent manner. Also, in chick chorioallantoic membrane assay, γ-tocotrienol significantly reduced the blood vessels formation. We further noticed that γ-tocotrienol blocked angiogenesis in an in vivo matrigel plug assay. Furthermore, γ-tocotrienol inhibited VEGF-induced autophosphorylation of VEGFR2 in HUVECs and also suppressed the constitutive activation of AKT/mammalian target of rapamycin (mTOR) signal transduction cascades in HUVECs as well as in HCC cells. Interestingly, γ-tocotrienol was also found to significantly reduce the tumor growth in an orthotopic HCC mouse model and inhibit tumor-induced angiogenesis in HCC patient xenografts through the suppression of various biomarkers of proliferation and angiogenesis. Taken together, our findings strongly suggest that γ-tocotrienol might be a promising anti-angiogenic drug with significant antitumor activity in HCC. |
| first_indexed | 2025-11-14T07:18:52Z |
| format | Journal Article |
| id | curtin-20.500.11937-16896 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:18:52Z |
| publishDate | 2014 |
| publisher | Impact Journals LLC |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-168962017-05-30T08:10:08Z γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model Siveen, K. Ahn, K. Ong, T. Shanmugam, M. Li, F. Yap, W. Kumar, Alan Prem Fong, C. Tergaonkar, V. Hui, K. Sethi, G. Angiogenesis is one of the key hallmarks of cancer. In this study, we investigated whether γ-tocotrienol can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and if so, through what molecular mechanisms. We observed that γ-tocotrienol inhibited vascular endothelial growth factor (VEGF)-induced migration, invasion, tube formation and viability of HUVECs in vitro. Moreover, γ-tocotrienol reduced the number of capillary sprouts from matrigel embedded rat thoracic aortic ring in a dose-dependent manner. Also, in chick chorioallantoic membrane assay, γ-tocotrienol significantly reduced the blood vessels formation. We further noticed that γ-tocotrienol blocked angiogenesis in an in vivo matrigel plug assay. Furthermore, γ-tocotrienol inhibited VEGF-induced autophosphorylation of VEGFR2 in HUVECs and also suppressed the constitutive activation of AKT/mammalian target of rapamycin (mTOR) signal transduction cascades in HUVECs as well as in HCC cells. Interestingly, γ-tocotrienol was also found to significantly reduce the tumor growth in an orthotopic HCC mouse model and inhibit tumor-induced angiogenesis in HCC patient xenografts through the suppression of various biomarkers of proliferation and angiogenesis. Taken together, our findings strongly suggest that γ-tocotrienol might be a promising anti-angiogenic drug with significant antitumor activity in HCC. 2014 Journal Article http://hdl.handle.net/20.500.11937/16896 http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1876 Impact Journals LLC fulltext |
| spellingShingle | Siveen, K. Ahn, K. Ong, T. Shanmugam, M. Li, F. Yap, W. Kumar, Alan Prem Fong, C. Tergaonkar, V. Hui, K. Sethi, G. γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model |
| title | γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model |
| title_full | γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model |
| title_fullStr | γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model |
| title_full_unstemmed | γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model |
| title_short | γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model |
| title_sort | γ-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of akt/mtor pathway in an orthotopic mouse model |
| url | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1876 http://hdl.handle.net/20.500.11937/16896 |