| Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits HIV-1 Tat-induced angiogenesis in Kaposi's sarcoma cells. | |
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MedLine Citation:
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PMID: 17868650 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released from KS and host cells and HIV viral products-the protein Tat are reported to be involved in angiogenesis. Mounting evidence further suggests that multiple angiogenic activities of Tat contribute to AIDS-associated Kaposi's sarcoma (AIDS-KS). Herein, we report that sulfated polymannuroguluronate (SPMG), a novel anti-AIDS drug candidate now undergoing phase II clinical trial, significantly eliminated Tat-induced angiogenesis in SLK cells both in vitro and in vivo. SPMG significantly and dose-dependently inhibits proliferation, migration, and tube formation by SLK cells. SPMG also dramatically arrested Tat-driven KDR phosphorylation and blocked the interaction between Tat and integrin beta1, thus inhibiting the phosphorylation of the downstream kinases of FAK, paxillin and MAPKs. In addition, SPMG was noted to block the release of bFGF and VEGF from ECM. All these collectively favor an issue that SPMG functions as a promising therapeutic against Tat-induced angiogenesis and pathologic events relevant to AIDS-KS, which adds novel mechanistic profiling to the anti-AIDS action of SPMG. |
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Authors:
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Cong-Xiao Lu; Jing Li; Yong-Xu Sun; Xin Qi; Qing-Juan Wang; Xian-Liang Xin; Mei-Yu Geng |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-16 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 74 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2007 Nov |
Date Detail:
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Created Date: 2007-10-01 Completed Date: 2007-11-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1330-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai 264000, and Department of Molecular Pharmacology, Marine Drug and Food Institute, School of Medicine and Pharmacy, Ocean University of China, Qingdao, PR China. lucongxiao2005@yahoo.com.cn |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-HIV Agents / administration & dosage, pharmacology*, therapeutic use Cell Adhesion / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Collagen Disease Models, Animal Dose-Response Relationship, Drug Drug Combinations Escherichia coli / genetics Fibroblast Growth Factor 2 / metabolism Gene Products, tat / biosynthesis, pharmacology* Glutathione Transferase / metabolism HIV-1 / metabolism* Humans Laminin Male Mice Neovascularization, Pathologic / drug therapy*, metabolism Polysaccharides / administration & dosage, pharmacology*, therapeutic use Proteoglycans Recombinant Fusion Proteins / biosynthesis, pharmacology* Sarcoma, Kaposi* / blood supply, metabolism, pathology Vascular Endothelial Growth Factor A / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Drug Combinations; 0/Gene Products, tat; 0/Laminin; 0/Polysaccharides; 0/Proteoglycans; 0/Recombinant Fusion Proteins; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/sulfated polymannuroguluronate; 103107-01-3/Fibroblast Growth Factor 2; 119978-18-6/matrigel; 9007-34-5/Collagen; EC 2.5.1.18/Glutathione Transferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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