title: Tricyclodecan-9-yl-xanthogenate (D609) mechanism of actions: a mini-review of literature.
abstract: 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. Zn²⁺ is necessary for PC-PLC enzymatic activity; inhibition by D609 might be attributed to its Zn²⁺ 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.
authors.affiliation: Department of Neurological Surgery, Clinical Science Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792-3232, USA. adibhatl@neurosurg.wisc.edu
authors.forename: Rao Muralikrishna
authors.initials: RM
authors.lastname: Adibhatla
authors.forename: J F
authors.initials: JF
authors.lastname: Hatcher
authors.forename: A
authors.initials: A
authors.lastname: Gusain
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D009636:Norbornanes; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001952:Bridged-Ring Compounds; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase
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