Reference - Detail
| RRC ID | 43488 |
|---|---|
| Author | Shibata A, Nakagawa K, Sookwong P, Tsuduki T, Tomita S, Shirakawa H, Komai M, Miyazawa T. |
| Title | Tocotrienol inhibits secretion of angiogenic factors from human colorectal adenocarcinoma cells by suppressing hypoxia-inducible factor-1alpha. |
| Journal | J Nutr |
| Abstract |
Tocotrienol (T3), unsaturated vitamin E, has recently gained considerable attention as a potent antiangiogenic agent minimizing tumor growth, the exact intracellular mechanisms of which remain poorly understood. Because hypoxia-inducible factor-1alpha (HIF-1alpha), its downstream target vascular endothelial growth factor (VEGF), and other angiogenic factors such as interleukin-8 (IL-8) and cyclooxygenase 2 (COX-2) play critical roles in neovascularization, we tested the hypothesis that the inhibitory effect of T3 on tumor angiogenesis is via regulation of these angiogenic factors. We used 2 cancer cell lines, human colorectal adenocarcinoma cells (DLD-1) and human hepatoma cells (HepG2). T3 isomers (2 micromol/L) inhibited hypoxia-induced VEGF secretion from DLD-1, with delta-T3 showing potent inhibition. Delta-T3 suppressed hypoxia-induced VEGF and IL-8 expression in DLD-1 at both mRNA and protein levels, and we found the inhibitory mechanism of delta-T3 by reducing HIF-1alpha protein expression or increasing HIF-1alpha degradation. Also, delta-T3 (2 micromol/L) did not affect hypoxia-induced COX-2 mRNA expression; however, delta-T3 tended to suppress (P = 0.044) hypoxia-induced COX-2 protein expression, implying a possible post-transcriptional mechanism by delta-T3. Overall, our results confirmed that T3 has an inhibitory effect on angiogenic factor secretion from cancer cells and revealed the possible mechanisms, providing new information about the antiangiogenic effects of T3. |
| Volume | 138(11) |
| Pages | 2136-42 |
| Published | 2008-11-1 |
| DOI | 10.3945/jn.108.093237 |
| PII | 138/11/2136 |
| PMID | 18936210 |
| MeSH | Angiogenic Proteins / genetics Angiogenic Proteins / metabolism* Antineoplastic Agents / pharmacology Cell Line, Tumor Colorectal Neoplasms / metabolism Gene Expression Regulation / drug effects Humans Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors* Hypoxia-Inducible Factor 1, alpha Subunit / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Tocotrienols / pharmacology* Transcription Factors / metabolism |
| IF | 4.281 |
| Times Cited | 57 |
| WOS Category | NUTRITION & DIETETICS |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Hep G2(RCB1648) |