https://scholars.lib.ntu.edu.tw/handle/123456789/564847
標題: | YC-1 inhibits HIF-1 expression in prostate cancer cells: Contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia | 作者: | Sun H.-L. Liu Y.-N. Huang Y.-T. Pan S.-L. Huang D.-Y. JIH-HWA GUH Lee F.-Y. Kuo S.-C. Teng C.-M. |
關鍵字: | Akt; HIF-1; NF-κB; Prostate cancer; YC-1 | 公開日期: | 2007 | 卷: | 26 | 期: | 27 | 起(迄)頁: | 3941-3951 | 來源出版物: | Oncogene | 摘要: | Hypoxia-inducible factor 1 (HIF-1), a transcription factor that is critical for tumor adaptation to microenvironmental stimuli, represents an attractive chemotherapeutic target. YC-1 is a novel antitumor agent that inhibits HIF-1 through previously unexplained mechanisms. In the present study, YC-1 was found to prevent HIF-1α and HIF-1β accumulation in response to hypoxia or mitogen treatment in PC-3 prostate cancer cells. Neither HIF-1α protein half-life nor mRNA level was affected by YC-1. However, YC-1 was found to suppress the PI3K/Akt/mTOR/4E-BP pathway, which serves to regulate HIF-1α expression at the translational step. We demonstrated that YC-1 also inhibited hypoxia-induced activation of nuclear factor (NF)-κB, a downstream target of Akt. Two modulators of the Akt/NF-κB pathway, caffeic acid phenethyl ester and evodiamine, were observed to decrease HIF-1α expression. Additionally, overexpression of NF-κB partly reversed the ability of wortmannin to inhibit HIF-1α-dependent transcriptional activity, suggesting that NF-κB contributes to Akt-mediated HIF-1α accumulation during hypoxia. Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression. ? 2007 Nature Publishing Group All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34249982595&doi=10.1038%2fsj.onc.1210169&partnerID=40&md5=b0d64d4c16faf39c2a758edbaef22215 https://scholars.lib.ntu.edu.tw/handle/123456789/564847 |
ISSN: | 9509232 | DOI: | 10.1038/sj.onc.1210169 | SDG/關鍵字: | 1 benzyl 3 (5 hydroxymethyl 2 furyl)indazole; caffeic acid; evodiamine; hypoxia inducible factor 1; hypoxia inducible factor 1alpha; hypoxia inducible factor 1beta; immunoglobulin enhancer binding protein; initiation factor 4E binding protein; mammalian target of rapamycin; messenger RNA; phosphatidylinositol 3 kinase; protein kinase B; wortmannin; article; controlled study; gene overexpression; human; human cell; hypoxia; male; molecular mechanics; priority journal; prostate cancer; protein expression; RNA translation; signal transduction; transcription regulation; 1-Phosphatidylinositol 3-Kinase; Aryl Hydrocarbon Receptor Nuclear Translocator; Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Guanylate Cyclase; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; I-kappa B Kinase; Indazoles; Male; Mitogens; NF-kappa B; Phosphorylation; Prostatic Neoplasms; Protein Kinases; Proto-Oncogene Proteins c-akt; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction |
顯示於: | 藥學系 |
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