Department of Pathology, Georg August University, D-37075 Göttingen, Germany.
Int J Oncol. 2013 Nov;43(5):1385-94. doi: 10.3892/ijo.2013.2060. Epub 2013 Aug 20.
Phytoestrogens have been shown to exert anti-proliferative effects on different cancer cells. In addition it could be demonstrated that inhibition of proliferation is associated with downregulation of the known stem cell factors NANOG, POU5F1 and SOX2 in tumor cells. We demonstrate the potential of Belamcanda chinensis extract (BCE) and tectorigenin as anticancer drugs in cell lines of malignant testicular germ cell tumor cells (TGCT) by inhibition of proliferation and regulating the expression of stem cell factors. The TGCT cell lines TCam-2 and NTera-2 were treated with BCE or tectorigenin and MTT assay was used to measure the proliferation of tumor cells. In addition, the expression of stem cell factors was analyzed by quantitative PCR and western blot analysis. Furthermore, global expression analysis was performed by microarray technique. BCE and tectorigenin inhibited proliferation and downregulated the stem cell factors NANOG and POU5F1 in TGCT cells. In addition, gene expression profiling revealed induction of genes important for the differentiation and inhibition of oncogenes. Utilizing connectivity map in an attempt to elucidate mechanism underlying BCE treatments we found highly positive association to histone deacetylase inhibitors (HDACi) amongst others. Causing no histone deacetylase inhibition, the effects of BCE on proliferation and stem cell factors may be based on histone-independent mechanisms such as direct hyperacetylation of transcription factors. Based on these findings, phytoestrogens may be useful as new agents in the treatment of TGCT.
植物雌激素已被证明对不同的癌细胞具有抗增殖作用。此外，研究表明，增殖抑制与肿瘤细胞中已知的干细胞因子 NANOG、POU5F1 和 SOX2 的下调有关。我们通过抑制增殖和调节干细胞因子的表达，证明了贝母提取物 (BCE) 和鸢尾黄素作为恶性睾丸生殖细胞肿瘤细胞 (TGCT) 细胞系抗癌药物的潜力。用 BCE 或鸢尾黄素处理 TGCT 细胞系 TCam-2 和 Ntera-2，并通过 MTT 测定法测量肿瘤细胞的增殖。此外，通过定量 PCR 和 Western blot 分析分析干细胞因子的表达。此外，通过微阵列技术进行了全基因表达分析。BCE 和鸢尾黄素抑制了 TGCT 细胞的增殖，并下调了干细胞因子 NANOG 和 POU5F1。此外，基因表达谱分析显示，分化和抑制癌基因的重要基因被诱导。利用连接图谱试图阐明 BCE 治疗的作用机制，我们发现与组蛋白去乙酰化酶抑制剂 (HDACi) 等高度正相关。BCE 对增殖和干细胞因子的作用不会引起组蛋白去乙酰化，可能基于组蛋白非依赖性机制，如转录因子的直接超乙酰化。基于这些发现，植物雌激素可能是治疗 TGCT 的新药物。
