phytoestrogens and Testicular-Neoplasms

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.

Topics: Biomarkers, Tumor; Blotting, Western; Cell Proliferation; Gene Expression Profiling; Humans; Isoflavones; Male; Neoplasms, Germ Cell and Embryonal; Oligonucleotide Array Sequence Analysis; Phytoestrogens; Plant Extracts; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stem Cell Factor; Testicular Neoplasms; Tumor Cells, Cultured

A few dietary studies have found elevated testicular cancer risks for higher red meat, fat, and milk intakes and lower intakes of fruits, vegetables, and fiber. Because hormonal modulation by dietary intake of plant estrogens could affect risk of testicular cancer, we chose to explore the possible relationship between dietary phytoestrogens and testicular cancer. We conducted a hospital-based case-control study of 159 testicular cancer cases diagnosed between 1990 and 1996 and 136 adult friend-matched controls at the University of Texas M. D. Anderson Cancer Center. Amounts of phytoestrogenic compounds in foods were added to the National Cancer Institute's DietSys program and then grouped into prelignans, lignans, flavonoids, isoflavonoids, phytosterols, and coumestrol for statistical analysis, expressed per 1,000 kcal. The results of multivariate logistic regression analysis showed, after adjustment for age, education, income, ethnicity, cryptorchidism, body mass index, baldness unrelated to therapy, severe acne in adolescence, early puberty, daily fiber and fat intake, and total daily calories, no discernable monotonic increased or decreased risk estimates across quartiles of phytoestrogen intake. A U-shaped pattern was observed for lignans and coumestrol. Further evaluation of this pattern by cubic spline parameterization did fit the data, but the data were also consistent with no effect. This hypothesis-generating study does not support the premise that dietary phytoestrogens increase or decrease testicular cancer risk in young men.

Topics: Adolescent; Adult; Anticarcinogenic Agents; Case-Control Studies; Estrogens, Non-Steroidal; Food Analysis; Germinoma; Humans; Isoflavones; Logistic Models; Male; Middle Aged; Odds Ratio; Phytoestrogens; Plant Preparations; Seminoma; Surveys and Questionnaires; Testicular Neoplasms; United States