| Tricyclodecan-9-yl-Xanthogenate (D609) Mechanism of Actions: A Mini-Review of Literature. | |
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MedLine Citation:
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PMID: 22101393 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Tricyclodecan-9-yl-xanthogenate (D609) is known for its antiviral and antitumor properties. D609 actions are widely attributed to inhibiting phosphatidylcholine (PC)-specific phospholipase C (PC-PLC). D609 also inhibits sphingomyelin synthase (SMS). PC-PLC and/or SMS inhibition will affect lipid second messengers 1,2-diacylglycerol (DAG) and/or ceramide. Evidence indicates either PC-PLC and/or SMS inhibition affected the cell cycle and arrested proliferation, and stimulated differentiation in various in vitro and in vivo studies. Xanthogenate compounds are also potent antioxidants and D609 reduced Aß-induced toxicity, attributed to its antioxidant properties. Zn(2+) is necessary for PC-PLC enzymatic activity; inhibition by D609 might be attributed to its Zn(2+) chelation. D609 has also been proposed to inhibit acidic sphingomyelinase or down-regulate hypoxia inducible factor-1α; however these are down-stream events related to PC-PLC inhibition. Characterization of the mammalian PC-PLC is limited to inhibition of enzymatic activity (frequently measured using Amplex red assay with bacterial PC-PLC as a standard). The mammalian PC-PLC has not been cloned; sequenced and structural information is unavailable. D609 showed promise in cancer studies, reduced atherosclerotic plaques (inhibition of PC-PLC) and cerebral infarction after stroke (PC-PLC or SMS). D609 actions as an antagonist to pro-inflammatory cytokines have been attributed to PC-PLC. The purpose of this review is to comprehensively evaluate the literature and summarize the findings and relevance to cell cycle and CNS pathologies. |
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Authors:
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Rao Muralikrishna Adibhatla; J F Hatcher; A Gusain |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-22 |
Journal Detail:
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Title: Neurochemical research Volume: - ISSN: 1573-6903 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7613461 Medline TA: Neurochem Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Neurological Surgery, H4-330, Clinical Science Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53792-3232, USA, adibhatl@neurosurg.wisc.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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