Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways.
Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways.
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DOI：
10.3892/or.15.6.1581
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发表时间：
2006-06
期刊：
影响因子：
4.2
通讯作者：
Yang Yang-Yang;T. Ikezoe;T. Takeuchi;Y. Adachi;Y. Ohtsuki;H. Koeffler;H. Taguchi
中科院分区：
文献类型：
--
作者：
Yang Yang-Yang;T. Ikezoe;T. Takeuchi;Y. Adachi;Y. Ohtsuki;H. Koeffler;H. Taguchi
Zanthoxyli Fuctus属于橙科，在包括日本在内的亚洲国家被用作调味品。本研究通过台盼蓝排斥试验，发现花椒水提物在体外对多种癌细胞具有抗肿瘤活性，包括前列腺癌(LNCaP，DU145，PC-3)、乳腺癌细胞(MCF-7，T47D，MDA-MB231)、肺癌细胞(NCI-H460，-H520)以及白血病细胞(HL-60，NB4，Jurkat)。重要的是，Zanthoxyli Fuctus减缓了BALB/c裸鼠体内移植的LNCaP、DU145和MDA-MB231细胞的增殖，而没有不良反应。进一步的研究探索了花椒抑制雄激素依赖型人前列腺癌LNCaP细胞增殖的分子机制，因为花椒对这些细胞具有最强的抗肿瘤活性。通过报告实验、Western印迹分析和TUNEL实验，花椒阻断雄激素受体(AR)信号转导，下调AR的核水平，并诱导这些细胞的凋亡。正如预期的那样，花椒果子还降低了这些细胞中AR靶分子--前列腺特异性抗原的水平。此外，以GSK-3α/β为底物的AKT激酶活性测定和Western印迹分析表明，花椒果糖能抑制AKT蛋白的表达，下调细胞周期蛋白D1的表达。综上所述，花椒可能会作为一种辅助治疗剂用于治疗各种癌症类型的个体。
Zanthoxyli Fructus belongs to the family of oranges and is used as a seasoning in Asian countries including Japan. This study found that a water extract of Zanthoxyli Fructus possessed anti-tumor activity against a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC-3), breast (MCF-7, T47D, MDA-MB231), lung (NCI-H460, -H520), as well as leukemia (HL-60, NB4, Jurkat) in vitro, as measured by the trypan blue exclusion test. Importantly, Zanthoxyli Fructus slowed the proliferation of LNCaP, DU145, and MDA-MB231 cells present as xenografts in BALB/c nude mice without adverse effects. Further studies explored the molecular mechanism by which Zanthoxyli Fructus inhibited the proliferation of androgen-dependent human prostate cancer LNCaP cells because Zanthoxyli Fructus possessed the strongest anti-tumor activity against these cells. Zanthoxyli Fructus blocked androgen receptor (AR) signaling in conjunction with down-regulation of nuclear levels of AR and induced apoptosis of these cells, as measured by the reporter assay, Western blot analysis, and TUNEL assay, respectively. As expected, Zanthoxyli Fructus also decreased the level of the AR-target molecule, prostate-specific antigen in these cells. Furthermore, Zanthoxyli Fructus inhibited AKT kinase and down-regulated levels of cyclin D1 protein, as measured by the AKT kinase assay with GSK-3alpha/beta as a substrate and Western blot analysis, respectively. Taken together, Zanthoxyli Fructus might be useful as an adjunctive therapeutic agent for the treatment of individuals with a variety of cancer types.