Anticancer effects of tanshinone I in human non-small cell lung cancer
Anticancer effects of tanshinone I in human non-small cell lung cancer
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DOI：
10.1158/1535-7163.mct-07-2288
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发表时间：
2008-11-01
影响因子：
5.7
通讯作者：
Chen, Jeremy J. W.
中科院分区：
文献类型：
--
作者：
Lee, Chen-Yu;Sher, Hui-Fang;Chen, Jeremy J. W.
丹参酮是丹参根的主要生物活性化合物，在中国传统医学中被用于许多治疗药物。我们研究了丹参酮对高侵袭性人肺腺癌细胞cl1 -5的抗癌作用。丹参酮I在体外显著抑制巨噬细胞条件下培养基刺激的CL - 1-5细胞的迁移、侵袭和明胶酶活性，并减少CL - 1-5携带严重联合免疫缺陷小鼠的肿瘤发生和转移。与诱导细胞凋亡的丹参酮IIA不同，丹参酮I没有直接的细胞毒性。实时定量PCR、荧光素酶报告实验和电泳迁移转移实验显示，丹参酮I通过降低条件培养基刺激的CL - 1-5细胞中激活蛋白-1和核因子- κ B的dna结合活性，降低了参与肿瘤转移的血管生成因子白介素-8的转录活性。肿瘤相关基因的微阵列和通路分析发现了丹参酮1应答的差异表达基因，这些基因可能与ras -丝裂原活化蛋白激酶和Rac1信号通路有关。这些结果表明，丹参酮I在体外和体内均具有抗癌作用，这些作用至少部分是通过白细胞介素-8、ras -丝裂原活化蛋白激酶和Rac1信号通路介导的。虽然丹参酮1具有显著的抗癌作用，但其潜在的抗凝作用应引起重视和评价。[j]；[7] (11):3527 - 38]
Tanshinones are the major bioactive compounds of Salvia miltiorrhiza Bunge (Danshen) roots, which are used in many therapeutic remedies in Chinese traditional medicine. We investigated the anticancer effects of tanshinones on the highly invasive human lung adenocarcinoma cell line, CL 1-5. Tanshinone I significantly inhibited migration, invasion, and gelatinase activity in macrophage-conditioned medium-stimulated CL 1-5 cells in vitro and also reduced the tumorigenesis and metastasis in CL 1-5-bearing severe combined immunodeficient mice. Unlike tanshinone IIA, which induces cell apoptosis, tanshinone I did not have direct cytotoxicity. Real-time quantitative PCR, luciferase reporter assay, and electrophoretic mobility shift assay revealed that tanshinone I reduces the transcriptional activity of interleukin-8, the angiogenic factor involved in cancer metastasis, by attenuating the DNA-binding activity of activator protein-1 and nuclear factor-kappa B in conditioned medium-stimulated CL 1-5 cells. Microarray and pathway analysis of tumor-related genes identified the differentially expressed genes responding to tanshinone 1, which may be associated with the Ras-mitogen-activated protein kinase and Rac1 signaling pathways. These results suggest that tanshinone I exhibits anticancer effects both in vitro and in vivo and that these effects are mediated at least partly through the interleukin-8, Ras-mitogen-activated protein kinase, and Rac1 signaling pathways. Although tanshinone I has a remarkable anticancer action, its potential anticoagulant effect should be noted and evaluated. [Mol Cancer Ther 2008;7(11):3527 - 38]