國家衛生研究院 NHRI:Item 3990099045/8153
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    題名: High effectiveness of triptolide, an active diterpenoid triepoxide, in suppressing Kir-channel currents from human glioma cells
    作者: So, EC;Lo, YC;Chen, LT;Kao, CA;Wu, SN
    貢獻者: National Institute of Cancer Research
    摘要: Triptolide (Trip), a diterpene triepoxide isolated from medicinal vine Trypterygium wilfordii Hook. F. possessed multiple biological activities including antineoplastic actions. However, no report concerning its effects on ion currents has been published. In this study, we attempted to determine whether this compound has any effects on ion currents in malignant glioma cells. The mRNA expression of KCNJ10 (Kir4.1) was detected in U373 glioma cells. The inwardly rectifying K+ currents (IK(IR)) in U373 cells were almost fully blocked by BaCl2 (1mM). Trip (30nM-10muM) effectively decreased the amplitude of IK(IR) in a concentration-dependent manner with an IC50 value of 0.72muM. In chlorotoxin-treated U373 cells, Trip-mediated block of IK(IR) remained effective. Addition of Trip (3muM) slightly inhibited the amplitude of Ca2+-activated K+ current and sustained K+ outward current in U373 cells. In cell-attached configuration, when Trip was added to the bath, the activity of inwardly rectifying K+ (Kir) channels diminished with no change in single-channel conductance. Its suppression of Kir channels was accompanied by a reduction in the slow component of mean open time. Under current-clamp conditions, addition of Trip depolarized the membrane along with changes in frequency histogram of resting potential. Block by this component of Kir4.1 channels may be an important mechanism underlying its actions on the functional activity of glioma cells. Targeting at Kir4.1 channels may be clinically useful as an adjunctive regimen to anti-cancer drugs.
    日期: 2014-09
    關聯: European Journal of Pharmacology. 2014 Sep;738:332-341.
    Link to: http://dx.doi.org/10.1016/j.ejphar.2014.05.059
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2999&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000339998000042
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84927171769
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