Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma
Constitutive activation of proinflammatory transcription factors such as STAT3 and NF-kB plays a pivotal role in the proliferation and survival of squamous cell carcinoma of the head and neck (HNSCC). Thus, the agents that can modulate deregulated STAT3 and NF-kB activation have a great potential bo...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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American Association for Cancer Research
2013
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/39026 |
| _version_ | 1848755478900768768 |
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| author | Li, F. Shanmugam, M. Chen, L. Chatterjee, S. Basha, J. Kumar, Alan Prem Kundu, T. Sethi, G. |
| author_facet | Li, F. Shanmugam, M. Chen, L. Chatterjee, S. Basha, J. Kumar, Alan Prem Kundu, T. Sethi, G. |
| author_sort | Li, F. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Constitutive activation of proinflammatory transcription factors such as STAT3 and NF-kB plays a pivotal role in the proliferation and survival of squamous cell carcinoma of the head and neck (HNSCC). Thus, the agents that can modulate deregulated STAT3 and NF-kB activation have a great potential both for the prevention and treatment of HNSCC. In the present report, we investigated the potential effects of garcinol, an active component of Garcinia indica on various inflammatory mediators involved in HNSCC progression using cell lines and xenograft mouse model. We found that garcinol inhibited constitutively activated STAT3in HNSCC cells in a time- and dose-dependent manner, which correlated with the suppression of the upstream kinases (c-Src, JAK1, and JAK2) in HNSCC cells. Also, we noticed that the generation of reactive oxygen species is involved in STAT3 inhibitory effect of garcinol. Furthermore, garcinol exhibited an inhibitory effect on the constitutive NF-kB activation, mediated through the suppression of TGF-b–activated kinase 1 (TAK1) and inhibitor of IkB kinase (IKK) activation in HNSCC cells. Garcinol also downregulated the expression of various gene products involved in proliferation, survival, and angiogenesis that led to the reduction of cell viability and induction of apoptosis in HNSCC cells. When administered intraperitoneally, garcinol inhibited the growth of human HNSCC xenograft tumors in male athymic nu/nu mice. Overall, our results suggest for the first time that garcinol mediates its antitumor effects in HNSCC cells and mouse model through the suppression of multiple proinflammatory cascades. |
| first_indexed | 2025-11-14T08:56:57Z |
| format | Journal Article |
| id | curtin-20.500.11937-39026 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:56:57Z |
| publishDate | 2013 |
| publisher | American Association for Cancer Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-390262023-02-22T06:24:18Z Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma Li, F. Shanmugam, M. Chen, L. Chatterjee, S. Basha, J. Kumar, Alan Prem Kundu, T. Sethi, G. HNSCC Cancer Carcinoma Constitutive activation of proinflammatory transcription factors such as STAT3 and NF-kB plays a pivotal role in the proliferation and survival of squamous cell carcinoma of the head and neck (HNSCC). Thus, the agents that can modulate deregulated STAT3 and NF-kB activation have a great potential both for the prevention and treatment of HNSCC. In the present report, we investigated the potential effects of garcinol, an active component of Garcinia indica on various inflammatory mediators involved in HNSCC progression using cell lines and xenograft mouse model. We found that garcinol inhibited constitutively activated STAT3in HNSCC cells in a time- and dose-dependent manner, which correlated with the suppression of the upstream kinases (c-Src, JAK1, and JAK2) in HNSCC cells. Also, we noticed that the generation of reactive oxygen species is involved in STAT3 inhibitory effect of garcinol. Furthermore, garcinol exhibited an inhibitory effect on the constitutive NF-kB activation, mediated through the suppression of TGF-b–activated kinase 1 (TAK1) and inhibitor of IkB kinase (IKK) activation in HNSCC cells. Garcinol also downregulated the expression of various gene products involved in proliferation, survival, and angiogenesis that led to the reduction of cell viability and induction of apoptosis in HNSCC cells. When administered intraperitoneally, garcinol inhibited the growth of human HNSCC xenograft tumors in male athymic nu/nu mice. Overall, our results suggest for the first time that garcinol mediates its antitumor effects in HNSCC cells and mouse model through the suppression of multiple proinflammatory cascades. 2013 Journal Article http://hdl.handle.net/20.500.11937/39026 10.1158/1940-6207.CAPR-13-0070 American Association for Cancer Research unknown |
| spellingShingle | HNSCC Cancer Carcinoma Li, F. Shanmugam, M. Chen, L. Chatterjee, S. Basha, J. Kumar, Alan Prem Kundu, T. Sethi, G. Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| title | Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| title_full | Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| title_fullStr | Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| title_full_unstemmed | Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| title_short | Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| title_sort | garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma |
| topic | HNSCC Cancer Carcinoma |
| url | http://hdl.handle.net/20.500.11937/39026 |