國家衛生研究院 NHRI:Item 3990099045/2896
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    题名: A G-quadruplex ligand 3,3 '-diethyloxadicarbocyanine iodide induces mitochondrion-mediated apoptosis but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells
    作者: Li, CP;Huang, JH;Chang, AC;Hung, YM;Lin, CH;Chao, Y;Lee, SD;Whang-Peng, J;Huang, TS
    贡献者: National Institute of Cancer Research
    摘要: Purpose. The G-quadruplex ligand 3,3'-diethyloxadicarbocyanine iodide (DODC) was reported to enhance the apoptotic potency of pheochromocytoma PC-12 and leukemia HL-60 cells through the inhibition of telomerase activity. In this study, a mitochondrion-mediated apoptotic pathway was demonstrated as another cytotoxic mechanism for DODC action. Methods. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA laddering assays were performed to exhibit the cytotoxicity and apoptosis-inducing activity of DODC. Telomeric repeat amplification protocol (TRAP) assay was used to evaluate the effect of DODC on cellular telomerase. The mitochondrial uptake of probe 3,3'-dihexyloxacarbocyanine iodide was measured by flow cytometry. The mitochondrial proteomes were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Western blot analyses were adopted to demonstrate the change of the distribution of mitochondrial proteins. Results. DODC alone was able to induce apoptotic cell death but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells. Instead, we found evidence that DODC significantly affected cellular mitochondria. DODC inhibited the uptake of another mitochondrial probe 3,3'-dihexyloxacarbocyanine iodide. By proteomic comparative analysis, we found that DODC induced the increase of prohibitin level in the mitochondria, indicating the occurrence of mitochondrial perturbation. Moreover, DODC was found to induce the levels of p53 and an 18-kDa truncated Bax on mitochondria, which in turn potentiated the release of cytochrome c for activation of caspases. Conclusions. DODC induces NPC-TW01 cell apoptosis via a mitochondrion-mediated mechanism. This paper demonstrates another cytotoxic mechanism of DODC other than inhibition of telomerase.
    关键词: Chemistry, Multidisciplinary;Pharmacology & Pharmacy
    日期: 2004-01
    關聯: Pharmaceutical Research. 2004 Jan;21(1):93-100.
    Link to: http://dx.doi.org/10.1023/B:PHAM.0000012166.44521.1f
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0724-8741&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000188120800012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=1642457358
    显示于类别:[黃智興] 期刊論文
    [彭汪嘉康(1996-2007)] 期刊論文

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