Phytoestrogens regulate the proliferation and expression of stem cell factors in cell lines of malignant testicular germ cell tumors

Hasibeder,Astrid; Venkataramani,Vivek; Thelen,Paul; Radzun,Heinz-Joachim; Schweyer,Stefan

doi:10.3892/ijo.2013.2060

Phytoestrogens regulate the proliferation and expression of stem cell factors in cell lines of malignant testicular germ cell tumors

Authors:
- Astrid Hasibeder
- Vivek Venkataramani
- Paul Thelen
- Heinz-Joachim Radzun
- Stefan Schweyer
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Affiliations: Department of Pathology, Georg August University, D-37075 Göttingen, Germany, Department of Hematology and Oncology, Georg August University, D-37075 Göttingen, Germany, Department of Urology, Georg August University, D-37075 Göttingen, Germany
Published online on: August 20, 2013 https://doi.org/10.3892/ijo.2013.2060
Pages: 1385-1394
Copyright: © Hasibeder et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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.

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