کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1925253 1536354 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Minocycline inhibits angiogenesis in vitro through the translational suppression of HIF-1α
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Minocycline inhibits angiogenesis in vitro through the translational suppression of HIF-1α
چکیده انگلیسی


• Minocycline inhibits HIF-1α protein expression through suppression of protein translation.
• Minocycline exhibits anti-angiogenic property through suppression of HIF-1α expression.
• Minocycline inhibits protein translation through the suppression of mTOR signaling and phosphorylation of eIF2α.

Minocycline was recently found to be effective against cancer. However, the precise molecular mechanisms of minocycline in cancer are poorly understood. Hypoxia-inducible factor-1 (HIF-1, a heterodimeric transcription factor composed of HIF-1α and β) activates the transcription of genes that are involved in angiogenesis in cancer. In this study, we found that minocycline significantly inhibits HIF-1α protein expression and suppresses HIF-1 transcriptional activity. The tube formation assay showed that minocycline has anti-angiogenic activity and suppresses hypoxia-induced vascular endothelial growth factor (VEGF) expression. The metabolic labeling assay showed that minocycline reduces HIF-1α protein translation and global protein synthesis. In addition, minocycline suppresses mTOR signaling and increases the phosphorylation of eIF2α, which is known to be related to the translational regulation of HIF-1α expression. These findings collectively indicate that minocycline is a potential inhibitor of HIF-1α and provide new insight into the discovery of drugs for cancer treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 545, 1 March 2014, Pages 74–82
نویسندگان
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