کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8336902 | 1540646 | 2015 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
δ-Tocotrienol treatment is more effective against hypoxic tumor cells than normoxic cells: potential implications for cancer therapy
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کلمات کلیدی
PBSHIF-1αNIHPECAM-1CDK4DLD-1H&E - H & EAkt - آکتhypoxia inducible factor-1α - عامل القایی هیپوکسی 1αNational Institutes of Health - مؤسسات ملی بهداشتPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریplatelet endothelial cell adhesion molecule-1 - مولکول چسبندگی سلول اندوتلیال پلاکتی-1Hematoxylin and Eosin - هماتوکسیلین و ائوزینprotein kinase B - پروتئین کیناز Bcyclin-dependent kinase 4 - کییناز وابسته به سیکلین 4
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: δ-Tocotrienol treatment is more effective against hypoxic tumor cells than normoxic cells: potential implications for cancer therapy δ-Tocotrienol treatment is more effective against hypoxic tumor cells than normoxic cells: potential implications for cancer therapy](/preview/png/8336902.png)
چکیده انگلیسی
Tocotrienols, unsaturated forms of vitamin E, inhibit the proliferation of a variety of cancer cells and suppress angiogenesis. However, the mechanisms underlying those effects on cancer cell growth remain unclear especially under hypoxic conditions. In this study, we demonstrated that δ-tocotrienol (δ-T3) could be used as a novel anticancer agent against human colorectal adenocarcinoma (DLD-1) cells under both normoxic and hypoxic conditions. δ-T3 inhibited the growth of DLD-1 cells in a dose-dependent fashion by inducing cell cycle arrest and apoptosis. This effect was more potent under hypoxic than normoxic conditions. The anticancer effect of δ-T3 was achieved by its up-regulation of cyclin-dependent kinase inhibitors (p21 and p27), the activation of caspases and the suppression of phosphorylation of protein kinase B (Akt) at Thr308 and Ser473. In in vivo studies, oral administration of rice bran tocotrienol (RBT3, mainly γ-T3) (10 mg/mouse/day) significantly inhibited tumor growth in nude mice. In tumor analyses, RBT3 activated p21, p27, caspase-3 and caspase-9 and decreased Akt phosphorylation. Furthermore, immunostaining revealed that RBT3 decreased the number of cells positive for CD31/platelet endothelial cell adhesion molecule-1 in microvessels in the tumor. Taken together, these data suggest that tocotrienols are potent antitumor agents capable of inducing apoptosis and inhibiting angiogenesis under both hypoxic and normoxic conditions. Tocotrienols could have significant therapeutic potential in the clinical treatment of tumors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 26, Issue 8, August 2015, Pages 832-840
Journal: The Journal of Nutritional Biochemistry - Volume 26, Issue 8, August 2015, Pages 832-840
نویسندگان
Akira Shibata, Kiyotaka Nakagawa, Tsuyoshi Tsuduki, Teruo Miyazawa,