Tocotrienol Inhibits Secretion of Angiogenic Factors from Human Colorectal Adenocarcinoma Cells by Suppressing Hypoxia-Inducible Factor-1{alpha}  

Oleh:

Shibata, Akira ; Nakagawa, Kiyotaka ; Sookwong, Phumon ; Tsuduki, Tsuyoshi ; Tomita, Shuhei

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 138 no. 11 (Nov. 2008), page 2136.
Topik: Nutrition and Disease

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2008.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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-1{alpha} (HIF-1{alpha}), 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 µmol/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-1{alpha} protein expression or increasing HIF-1{alpha} degradation. Also, {delta}-T3 (2 µmol/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.

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