title: Minocycline inhibits angiogenesis in vitro through the translational suppression of HIF-1α.
abstract: 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.
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Hui-Jung
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Incheol
authors.initials: I
authors.lastname: Seo
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Jha
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Suh
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea. Electronic address: wonki@dsmc.or.kr.
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Baek
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000900:Anti-Bacterial Agents; D015852:Eukaryotic Initiation Factor-2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D008911:Minocycline
keywords: HIF-1; Minocycline; VEGF; mTOR