首页> 外文期刊>Biochimica et Biophysica Acta. General Subjects >Streptonigrin inhibits beta-Catenin/Tcf signaling and shows cytotoxicity in beta-catenin-activated cells.
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Streptonigrin inhibits beta-Catenin/Tcf signaling and shows cytotoxicity in beta-catenin-activated cells.

机译:链霉菌素抑制β-连环蛋白/ Tcf信号传导,并在β-连环蛋白激活的细胞中显示出细胞毒性。

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BACKGROUND: Activation of beta-catenin/T-cell factor (Tcf) signaling plays a role in human carcinogenesis. This suggests a possibility that the beta-catenin/Tcf signaling activated by the accumulation of beta-catenin in the nucleus is related to some type of human carcinogenesis. Therefore, if beta-catenin's transcriptional activity can be markedly down-regulated, tumor growth will be suppressed in beta-catenin activated types of cancer. METHODS: To investigate the activation or suppression of beta-catenin/Tcf transcription, we established a transiently transfected cell line with a constitutively active beta-catenin mutant gene whose product is not degraded. This cell line was also co-transfected with luciferase reporter gene constructs containing either an optimized (TOPflash) or mutant (FOPflash) Tcf-binding element. RESULTS: We identified the inhibitory effect of streptonigrin against beta-catenin/Tcf signaling in beta-catenin activated cells. Streptonigrin inhibited the transcriptional activity of beta-catenin/Tcf in SW480 cells and HEK293 cells transiently transfected with a constitutively active mutant beta-catenin gene. The growth inhibitory effect of streptonigrin was more evident in beta-catenin-activated cancer cells than in non-activated cancer cells. The electrophoresis mobility shift assay showed that the binding of Tcf complexes with their specific DNA-binding sites was suppressed by streptonigrin. Conclusion: Streptonigrin is a negative regulator of beta-catenin/Tcf signaling, and their inhibitory mechanism is related to the proliferation inhibitory effect on beta-catenin-activated cancer cells. GENERAL SIGNIFICANCE: This report reveals a molecular mechanism underlying the anti-tumor effect of streptonigrin from the perspective beta-catenin/Tcf signaling. Given its function in inhibiting beta-catenin/Tcf signaling, streptonigrin may be of interest as a leading compound for chemotherapeutic agent against beta-catenin-activated tumorigenesis.
机译:背景:β-catenin/ T细胞因子(Tcf)信号的激活在人类致癌作用中发挥作用。这表明由β-连环蛋白在细胞核中积累激活的β-连环蛋白/ Tcf信号传导可能与某种类型的人类致癌作用有关。因此,如果可以显着下调β-catenin的转录活性,那么在β-catenin激活类型的癌症中,肿瘤的生长将受到抑制。方法:为了研究β-catenin/ Tcf转录的激活或抑制,我们建立了一个具有组成型活性β-catenin突变基因的瞬时转染细胞系,该产物的产物未降解。该细胞系还与含有优化的(TOPflash)或突变的(FOPflash)Tcf结合元件的荧光素酶报道基因构建体共转染。结果:我们鉴定了链霉菌素对β-catenin活化细胞中β-catenin/ Tcf信号转导的抑制作用。链霉菌素抑制SW480细胞和用组成型活性突变体β-catenin基因瞬时转染的HEK293细胞中β-catenin/ Tcf的转录活性。链霉菌素的生长抑制作用在β-catenin激活的癌细胞中比在未激活的癌细胞中更明显。电泳迁移率变动分析表明,链霉菌素抑制了Tcf复合物与其特定DNA结合位点的结合。结论:链霉菌素是β-catenin/ Tcf信号转导的负调节剂,其抑制机制与β-catenin活化的癌细胞的增殖抑制作用有关。一般意义:该报告从β-catenin/ Tcf信号的角度揭示了链霉菌素抗肿瘤作用的分子机制。鉴于其在抑制β-catenin/ Tcf信号传导中的功能,链霉菌素可能是对抗β-catenin激活的肿瘤发生的化学治疗药物的领先化合物。

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