https://scholars.lib.ntu.edu.tw/handle/123456789/632384
Title: | Macrophage Migration Inhibitory Factor Acts as the Potential Target of a Newly Synthesized Compound, 1-(9′-methyl-3′-carbazole)-3, 4-dihydro-β-carboline | Authors: | Ko P.-H Shen Y.-C Murugan K Huang C.-W Sivakumar G Pal P Liao C.-C Luo K.-S ERIC YAO-YU CHUANG MONG-HSUN TSAI LIANG-CHUAN LAI |
Issue Date: | 2019 | Journal Volume: | 9 | Journal Issue: | 1 | Source: | Scientific Reports | Abstract: | For a newly synthesized compound, identifying its target protein is a slow but pivotal step toward understand its pharmacologic mechanism. In this study, we systemically synthesized novel manzamine derivatives and chose 1-(9′-methyl-3′-carbazole)-3, 4-dihydro-β-carboline (MCDC) as an example to identify its target protein and function. MCDC had potent toxicity against several cancer cells. To identify its target protein, we first used a docking screen to predict macrophage migration inhibitory factor (MIF) as the potential target. Biochemical experiments, including mutation analysis and hydrogen-deuterium exchange assays, validated the binding of MCDC to MIF. Furthermore, MCDC was shown by microarrays to interfere with the cell cycle of breast cancer MCF7 cells. The activated signaling pathways included AKT phosphorylation and S phase-related proteins. Our results showed MIF as a potential direct target of a newly synthesized manzamine derivative, MCDC, and its pharmacologic mechanisms. © 2019, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061588647&doi=10.1038%2fs41598-019-38590-y&partnerID=40&md5=607c39c9f8d124dee07b77b490c40105 https://scholars.lib.ntu.edu.tw/handle/123456789/632384 |
ISSN: | 20452322 | DOI: | 10.1038/s41598-019-38590-y | SDG/Keyword: | antineoplastic agent; carbazole derivative; carboline derivative; isomerase; macrophage migration inhibition factor; MIF protein, human; tumor marker; apoptosis; breast tumor; cell cycle; cell proliferation; chemistry; drug effect; female; gene expression profiling; gene expression regulation; human; metabolism; pathology; phosphorylation; tumor cell culture; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Breast Neoplasms; Carbazoles; Carbolines; Cell Cycle; Cell Proliferation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Phosphorylation; Tumor Cells, Cultured |
Appears in Collections: | 醫學系 |
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