Journal article
Garcinol, a Polyisoprenylated Benzophenone Modulates Multiple Proinflammatory Signaling Cascades Leading to the Suppression of Growth and Survival of Head and Neck Carcinoma
Cancer prevention research (Philadelphia, Pa.), Vol.6(8), pp.843-854
08/01/2013
DOI: 10.1158/1940-6207.CAPR-13-0070
PMID: 23803415
Abstract
Constitutive activation of proinflammatory transcription factors such as STAT3 and NF-kappa B 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-kappa B 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 STAT3 in 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-kappa B activation, mediated through the suppression of TGF-beta-activated kinase 1 (TAK1) and inhibitor of I kappa B 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.
Details
- Title: Subtitle
- Garcinol, a Polyisoprenylated Benzophenone Modulates Multiple Proinflammatory Signaling Cascades Leading to the Suppression of Growth and Survival of Head and Neck Carcinoma
- Creators
- Feng Li - National University of SingaporeMuthu K. Shanmugam - National University of SingaporeLuxi Chen - National University of SingaporeSnehajyoti Chatterjee - Jawaharlal Nehru Centre for Advanced Scientific ResearchJeelan Basha - Jawaharlal Nehru Centre for Advanced Scientific ResearchAlan Prem Kumar - National Cancer Centre SingaporeTapas K. Kundu - Jawaharlal Nehru Centre for Advanced Scientific ResearchGautam Sethi - National University of Singapore
- Resource Type
- Journal article
- Publication Details
- Cancer prevention research (Philadelphia, Pa.), Vol.6(8), pp.843-854
- DOI
- 10.1158/1940-6207.CAPR-13-0070
- PMID
- 23803415
- NLM abbreviation
- Cancer Prev Res (Phila)
- ISSN
- 1940-6207
- eISSN
- 1940-6215
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 12
- Grant note
- R-184-000-177-112 / NUS Academic Research Fund R-184-000-211-213 / National Medical Research Council of Singapore; National Medical Research Council, Singapore R-184-000-228-112 / Academic Research Fund Tier 1 R-713-000-142-112 / Singapore Ministry of Education Tier 2; Ministry of Education, Singapore Sir JC Bose National Fellowship, Department of Science and Technology, Government of India R-713-001-011-271 / Cancer Science Institute of Singapore, Experimental Therapeutics I Program
- Language
- English
- Date published
- 08/01/2013
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984303748502771
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