Targeting estrogen-related receptor alpha inhibits epithelial-to-mesenchymal transition and stem cell properties of ovarian cancer cells.

Epithelial-mesenchymal transition represents a key event in cancer progression and has emerged as a promising anticancer target. Estrogen-related receptor alpha (ERRα) is frequently elevated in advanced-stage ovarian cancer, but its potential role in tumor progression is not known. Here we show that ERRα functions in epithelial-mesenchymal transition and in subsequent stem cell traits responsible for the acquisition of high degree of aggressiveness and potential for metastasis that are characteristic of ovarian cancer. Importantly, targeted inhibition of ERRα also inhibited the expression of Snail, a repressor of E-cadherin and an inducer of epithelial-mesenchymal transition. Interestingly, induction of Snail resulted from not only changes in mRNA transcription rate but also mRNA stability. We thus identified the miR-200 family as a new player in the ERRα-mediated posttranscriptional regulation of Snail, and antagonism of miR-200a/b could revert the decreased expression of Snail and reversal of epithelial-mesenchymal transition and stem cell characteristics due to ERRα depletion. Finally, we showed that RNA interference-mediated inhibition of ERRα significantly reduced tumor burden, ascites formation, and metastatic peritoneal nodules in vivo in an orthotopic model of ovarian cancer. These results suggest ERRα activation as a mechanism of tumor aggressiveness and imply that targeting ERRα may be a promising approach in ovarian cancer treatment.

Ginseng and male reproductive function.

Ginseng is often referred to as the King of all herbs, and is found to be a promising agent to improve general well-being. Ginseng has also been reputed as an aphrodisiac, and is used to treat sexual dysfunction as well as to enhance sexual behavior in traditional Chinese medical practices. Data from animal studies have shown a positive correlation among ginseng, libido, and copulatory performances, and these effects have been confirmed in case-control studies in human. In addition, ginseng is found to improve the sperm quality and count of healthy individuals as well as patients with treatment-related infertility. These actions are mostly attributed to ginsenosides, the major pharmacological active components of ginseng. This review compiles the current knowledge about the multifaceted effects of ginseng on male reproductive function, and also focuses on its mechanisms of action that may represent novel therapeutic strategies for the treatment of male reproductive diseases or disorders.

Gonadotropin and its role in the ß-catenin/T-cell factor signaling pathway.

Gonadotropins, follicle-stimulating hormone and luteinizing hormone are key regulators in ovarian function, acting in an endocrine manner to regulate gametogenesis and steroidogenesis. In addition to normal tissue, gonadotropin receptors have also been demonstrated in ovarian carcinoma cell lines and primary tumors, suggesting that the gonadotropins may play a role in the pathophysiology of ovarian cancer. Thus, understanding mechanisms involved in signaling transduction by the gonadotropin receptors are of considerable interest and potential significance. In the ovary, gonadotropins initiate their cellular responses by binding to their G-protein-coupled receptors and activation of specific downstream intracellular effectors and signal pathways, including those of protein kinases A and C and mitogen-activated protein kinase. Recently, gonadotropins were shown to stimulate nuclear accumulation of ß-catenin, which controls lymphoid-enhancing factor/T-cell factor family-sensitive gene expression. ß-catenin has a pivotal function in the control of cell fate. The ability of gonadotropins to regulate ß-catenin provides a new dimension of knowledge linking pituitary hormones to the ß-catenin signaling in normal ovarian physiology and demonstrating how its dysregulation can contribute to the development of ovarian cancer.