Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells.

Metformin (MET) is increasingly implicated in reducing the incidence of multiple cancer types in patients with diabetes. However, similar effects of MET in non-diabetic women with endometrial cancer (EC) remain unknown. In a pilot study, obese non-diabetic women diagnosed with type 1, grade 1/2 EC, and consenting to participate were randomly assigned to receive MET or no MET (control (CON)) during the pre-surgical window between diagnosis and hysterectomy. Endometrial tumors obtained at surgery (MET, n = 4; CON, n = 4) were analyzed for proliferation (Ki67), apoptosis (TUNEL), and nuclear expression of ERα, PGR, PTEN, and KLF9 proteins in tumor glandular epithelial (GE) and stromal (ST) cells. The percentages of immunopositive cells for PGR and for KLF9 in GE and for PTEN in ST were higher while those for ERα in GE but not ST were lower, in tumors of MET vs. CON patients. The numbers of Ki67- and TUNEL-positive cells in tumor GE and ST did not differ between groups. In human Ishikawa endometrial cancer cells, MET treatment (60 µM) decreased cell numbers and elicited distinct temporal changes in ESR1, KLF9, PGR, PGR-B, KLF4, DKK1, and other tumor biomarker mRNA levels. In the context of reduced KLF9 expression (by siRNA targeting), MET rapidly amplified PGR, PGR-B, and KLF4 transcript levels. Our findings suggest that MET acts directly in EC cells to modify steroid receptor expression and signaling network and may constitute a preventative strategy against EC in high-risk non-diabetic women.

Diets Containing Shiitake Mushroom Reduce Serum Lipids and Serum Lipophilic Antioxidant Capacity in Rats.

BACKGROUND: We previously reported that dietary intake of shiitake mushroom (SM; Lentinus edodes) decreased serum concentrations of polar lipids in male rats. OBJECTIVE: This study evaluated the dietary effects of SM on serum cholesterol-related and serum antioxidant indexes in rats of both sexes. METHODS: Sprague-Dawley rats [38 dams and their offspring (20 males and 20 females/diet)] were fed diets containing 0 (control), 1%, 4%, or 10% (wt:wt) SM powder from gestation day 4 through to postnatal day (PND) 126. Biochemical indexes were monitored during the midgrowth phase (PNDs 50-66). RESULTS: The food consumption by offspring fed the control diet and diets supplemented with SM was not different when measured on PND 65. However, the 4% and 10% SM diets resulted in male rats with 7% lower body weights than those of the other 2 groups on PND 66. SM consumption dose-dependently decreased the concentrations of lipidemia-related factors in sera, irrespective of sex. At PND 50, serum concentrations of total cholesterol, HDL cholesterol, and non-HDL cholesterol in SM-fed male and female rats were generally lower (3-27%) than those in the corresponding control groups. Consumption of the 10% SM diet resulted in significantly decreased (55%) serum triglyceride concentrations relative to the control groups for both sexes. The 10% SM diet elicited a 62% reduction of serum leptin concentrations in females but not in males, and this same diet increased serum insulin (137%) and decreased serum glucose (15%) in males compared with controls. Serum lipophilic antioxidant capacity in males and females fed SM diets was generally lower (31-86%) than that in the control groups. CONCLUSION: SM decreased the concentrations of lipidemia-related factors in rat sera irrespective of sex. The SM-elicited reduction of lipophilic antioxidant capacity irrespective of sex may reflect a lower pro-oxidative state and, hence, improved metabolic profile.