Ginkgetin induces cell death in breast cancer cells via downregulation of the estrogen receptor.

Ginkgetin is a natural biflavonoid isolated from the leaves of Ginkgo biloba, and is characterized by its anti-inflammatory and anti-viral activities. Although numerous studies state that it has also antitumor activity, the anti-proliferative effect of ginkgetin and the underlying mechanism in breast cancer cells have not yet been investigated. In the present study, ginkgetin inhibited the cell viability of MCF-7 and T-47D cells dose-dependently, and suppressed the expression of the estrogen receptor (ER) at the mRNA and protein levels. Among the targets of the ER, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), cyclin D1 and survivin were also downregulated by ginkgetin treatment. The anti-proliferative effects of ginkgetin were sufficient to suppress the growth by estradiol stimulation. However, ginkgetin did not significantly affect the viability of MDA-MB-231 cells, which are ER-negative cells. Furthermore, the knockdown of the ER and an inhibitor of PFKFB3 significantly sensitized MCF-7 and T-47D cells to ginkgetin. These findings suggest that ginkgetin induces cell death in ER-positive breast cancer cells via the inhibition of ER expression and that it is a promising agent for breast cancer treatment.

Harmless effects of argon plasma on caudal fin regeneration and embryogenesis of zebrafish: novel biological approaches for safe medical applications of bioplasma

The argon plasma jet (Ar-PJ) is widely used in medical fields such as dermatology and dentistry, and it is considered a promising tool for cancer therapy. However, the in vivo effects of Ar-PJ for medical uses have not yet been investigated, and there are no biological tools to determine the appropriate clinical dosages of Ar-PJ. In this study, we used the caudal fin and embryo of zebrafish as novel in vivo tools to evaluate the biosafety of Ar-PJ. Typically, Ar-PJ is known to induce cell death in two-dimensional (2D) cell culture systems. By contrast, no detrimental effects of Ar-PJ were shown in our 3D zebrafish systems composed of 2D cells. The Ar-PJ-treated caudal fins grew by an average length of 0.7 mm, similar to the length of the normally regenerating fins. Remarkably, Ar-PJ did not affect the expression patterns of Wnt8a and β-Catenin, which play important roles in fin regeneration. In the embryo system, 85% of the Ar-PJ-treated embryos hatched, and the lateral length of these embryos was ~3.3 mm, which are equivalent to the lengths of normal embryos. In particular, vasculogenesis, which is the main cellular process during tissue regeneration and embryogenesis, occurred normally under the Ar-PJ dose used in this study. Therefore, our biosafety evaluation tools that use living model systems can be used to provide an experimental guideline to determine the clinically safe dosage of Ar-PJ.

Health Status and Health-promoting Lifestyle for Living Donors after Kidney Donation Through Survey / 대한이식학회지

BACKGROUND: Normal renal function and health have been recognized as important factors in living donors after kidney donation. The purpose of this study was to evaluate the health status and health-promoting lifestyle in living donors after kidney donation. METHODS: A total of 678 living-kidney donors were counted in our center from January 1990 to December 2011. Only 84 donors agreed to participate in the survey by telephone. We received consent for participation in our survey from 48 donors (57.1%). Data were collected from May to August 2013 using donor characteristics, health status, and Health Promoting Lifestyle Profile I (HPLP-I). RESULTS: The donors were predominantly female (62.5%) and the average age was 48.9+/-11.8 years, and the average period after nephrectomy was 9.7+/-5.7 years. The characteristics of donors included ideal body weight (37.5%), overweight (37.5%) in body mass index, and good health status (81.3%). Most donors underwent an annual medical check-up (56.2%), no health problem (81.3%), and no disease (64.6%). However, one patient was treated with dialysis for renal failure due to diabetes. The total average score for HPLP-I was 128.3+/-13.9. Higher than average scores (116.3+/-19.1) were observed for the general middle-aged woman. There were statistically significant differences in self-realization and nutrition in subsection of HPLP-I. Self-realization showed a higher score for Christian (F=2.743, P=0.041) and good health (F=3.389, P=0.017). Nutrition showed a higher score for overweight, obesity (F=6.783, P=0.000), and older than 60 (F=3.854, P=0.009). CONCLUSIONS: Most living kidney donors were healthy after their donation and had relatively high scores for health-promoting lifestyle. However, one patient had a serious health problem. In addition, younger, longer period after donation, and the rare health examination of donors showed a lower health-promoting lifestyle. Designed and continuous health-care management after transplantation is needed for kidney donors.

The homotrimeric structure of HtrA2 is indispensable for executing its serine protease activity

Serine protease activity of high temperature requrement 2 (HtrA2) is essential for promoting cell death, as well as for protecting against cellular stresses. An X-ray crystallographic study described the formation of a pyramid shaped homotrimer that is a proteolytically competent form of HtrA2; however, little is known about effects of the trimeric structure of HtrA2 on the natural substrates. In this study, we generated the HtrA2 protein that has a single point mutation at the homotrimerization motif to assess relationship between structure and the proteolytic activity of HtrA2 on its substrates. Using gel filtration, a native gel electrophoresis system, and a co-precipitation assay, we confirm that phenylalanine 149 in HtrA2 is a crucial determinant for the formation of the HtrA2 homotrimeric structure. Moreover, we described that the HtrA2 monomeric form abolished not only autoproteolytic activity, but also the proteolytic activity against XIAP (X-linked inhibitor of apoptosis protein) known as the HtrA2 substrate. Taken together, the results indicate that the homotrimeric structure of HtrA2 is required for executing its serine protease activity.