Antikanzerogene Effekte von Belamcanda chinensis in Zelllinien maligner Keimzelltumoren des Hodens

Anticancer activities of Belamcanda chinensis in cell lines of malignant testicular germ cell tumors

by Astrid Hasibeder
Doctoral thesis
Date of Examination:2013-11-06
Date of issue:2013-11-05
Advisor:PD Dr. Stefan Schweyer
Referee:PD Dr. Stefan Schweyer
Referee:PD Dr. Elmar Heinrich
Persistent Address: http://dx.doi.org/10.53846/goediss-4129

 

 

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Abstract

English

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, western blot analysis and immuncytochemistry. 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. Hormone receptors known to be effected in prostate cancer cells by BCE or tectorigenin were not regulated in TGCT cells. 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.
Keywords: phytoestrogens; testicular germ cell tumors; proliferation; stem cell factors
 
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