Stemona alkaloids,from traditional Thai medicine,increase chemosensitivity via P-glycoprotein-mediated multidrugresistance

Wisinee Chanmahasathien, Chadarat Ampasavate, Harald Greger, Pornngarm Limtrakul (Korresp. Autor*in)

    Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

    Abstract

    P-glycoprotein-mediated drugeffluxcancauseamultidrugresistance(MDR)phenotypethatisassociated with apoorresponsetocancerchemotherapy.Throughbioassay-guidedfractionation,active Stemona alkaloids wereisolatedfromtherootsof Stemona aphylla and S. burkillii. Thechemicalstructuresofiso- lated alkaloidswereconfirmedbyHPLC,LC–MSandNMRasstemocurtisineandoxystemokerrinefrom S. aphylla, andstemofolinefrom S. burkillii. Theisolatedalkaloidswereevaluatedforsynergisticgrowth inhibitory effectwithcancerchemotherapeuticagentsincludingvinblastine,paclitaxelanddoxorubicin of KB-V1cells(MDRhumancervicalcarcinomawithP-gpexpression),butnotinKB-3-1cells(drugsensi- tive humancervicalcarcinoma,whichlackP-gpexpression).Verapamilwasemployedasacomparative agent. Theresultsshowedthatamongthesethreeisolatedalkaloids;stemofolineexhibitedthemost potent effect in vitro in thereversalofP-gp-mediatedMDR.Treatmentwithstemofolineatthevari- ous concentrationsupto72hwasabletosignificantlyincreasesensitivityofanticancerdrugsincluding vinblastine, paclitaxelanddoxorubicinindose-andtime-dependentmannerinKB-V1cells.Theresult obtained fromthisstudyindicatedthat Stemona alkaloids mayplayanimportantroleasaP-gpmod- ulator asused in vitro and maybeeffectiveinthetreatmentofmultidrug-resistantcancers.Thisisthe first reportofnewpharmacologicalactivityof Stemona alkaloids, whichcouldbeanewpotentialMDR chemosensitizer.
    OriginalspracheEnglisch
    Seiten (von - bis)199-204
    Seitenumfang6
    FachzeitschriftPhytomedicine
    Ausgabenummer18
    PublikationsstatusVeröffentlicht - 2011

    ÖFOS 2012

    • 106002 Biochemie
    • 106034 Phytochemie

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