國家衛生研究院 NHRI:Item 3990099045/6646
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6646


    Title: Control of cyclooxygenase-2 expression and tumorigenesis by endogenous 5-methoxytryptophan
    Authors: Cheng, HH;Kuo, CC;Yan, JL;Chen, HL;Lin, WC;Wang, KH;Tsai, KKC;Guvén, H;Flaberg, E;Szekely, L;Klein, G;Wu, KK
    Contributors: Institute of Cellular and Systems Medicine;National Institute of Cancer Research
    Abstract: Cyclooxygenase-2 (COX-2) expression is induced by mitogenic and proinflammatory factors. Its overexpression plays a causal role in inflammation and tumorigenesis. COX-2 expression is tightly regulated, but the mechanisms are largely unclear. Here we show the control of COX-2 expression by an endogenous tryptophan metabolite, 5-methoxytryptophan (5-MTP). By using comparative metabolomic analysis and enzyme-immunoassay, our results reveal that normal fibroblasts produce and release 5-MTP into the extracellular milieu whereas A549 and other cancer cells were defective in 5-MTP production. 5-MTP was synthesized from l-tryptophan via tryptophan hydroxylase-1 and hydroxyindole O-methyltransferase. 5-MTP blocked cancer cell COX-2 overexpression and suppressed A549 migration and invasion. Furthermore, i.p. infusion of 5-MTP reduced tumor growth and cancer metastasis in a murine xenograft tumor model. We conclude that 5-MTP synthesis represents a mechanism for endogenous control of COX-2 overexpression and is a valuable lead for new anti-cancer and anti-inflammatory drug development.
    Date: 2012-08-14
    Relation: Proceedings of the National Academy of Sciences of the United States of America. 2012 Aug 14;109(33):13231-13236.
    Link to: http://dx.doi.org/10.1073/pnas.1209919109
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000307807000028
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84865190537
    Appears in Collections:[Kenneth Kun-Yu Wu] Periodical Articles
    [Cheng-Chin Kuo] Periodical Articles
    [Kelvin Kun-Chih Tsai] Periodical Articles

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