Abstract l -Mimosine, an iron chelator and a prolyl 4-hydroxylase inhibitor, blocks many cancer cells at the late G 1 phase. B-cell translocation gene 2 ( Btg2 ) regulates the G 1 /S transition phases of the cell cycle. N- myc downstream regulated gene 1 ( Ndrg1 ) is a differentiation-inducing gene upregulated by hypoxia. We evaluated the molecular mechanisms of l -mimosine on cell cycle modulation in PC-3 and LNCaP prostate carcinoma cells. The effect of l -mimosine on cell proliferation of prostate carcinoma cells was determined by the ( 3 H)thymidine incorporation and flow cytometry assays. l -Mimosine arrested the cell cycle at the G 1 phase in PC-3 cells and at the S phase in LNCaP cells, thus attenuating cell proliferation. Immunoblot assays indicated that hypoxia and l -mimosine stabilized hypoxia-inducible factor-1α (HIF-1α) and induced Btg2 and Ndrg1 protein expression, but downregulated protein levels of cyclin A in both PC-3 and LNCaP cells. l -Mimosine treatment decreased cyclin D1 protein in PC-3 cells, but not in LNCaP cells. Dimethyloxalylglycine, a pan-prolyl hydroxylase inhibitor, also induced Btg2 and Ndrg1 protein expression in LNCaP cells. The transient gene expression assay revealed that l -mimosine treatment or cotransfection with HIF-1α expression vector enhanced the promoter activities of Btg2 and Ndrg1 genes. Knockdown of HIF-1α attenuated the increasing protein levels of both Btg2 and Ndrg1 by hypoxia or l -mimosine in LNCaP cells. Our results indicated that hypoxia and l -mimosine modulated Btg2 and Ndrg1 at the transcriptional level, which is dependent on HIF-1α. l -Mimosine enhanced expression of Btg2 and Ndrg1 , which attenuated cell proliferation of the PC-3 and LNCaP prostate carcinoma cells. hypoxia hypoxia-inducible factor-1α iron chetomin cell cycle Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajpcell.​00180.​2011 Am J Physiol Cell Physiol February 2012 vol. 302 no. 4 C676-C685 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpcell.00180.2011v1 302/4/C676 most recent Classifications Growth, Differentiation, and Apoptosis Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Chung, L. Articles by Juang, H. PubMed PubMed citation Articles by Chung, L. Articles by Juang, H. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of Am J Physiol Cell Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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