İbrahim H. Özercan

Abstract Genistein, the major isoflavone in soybean, has been reported to exert anticancer effects on various types of cancer including ovarian cancer; however, its chemopreventive effects and mechanisms of action in ovarian cancer have not been fully elucidated in spontaneously developing ovarian cancer models. In this study, we demonstrated the preventive effects and mechanisms of genistein in the laying hen model that develops spontaneous ovarian cancer at high incidence rates. Laying hens were randomized to three groups: control (3.01 mg/hen, n = 100), low (52.48 mg/hen n = 100), and high genistein supplementation (106.26 mg/hen/day; per group). At the end of 78 weeks, hens were euthanized and ovarian tumors were collected and analyzed. We observed that genistein supplementation significantly reduced the ovarian tumor incidence (P = 0.002), as well as the number and size of the tumors (P = 0.0001). Molecular analysis of the ovarian tumors revealed that genistein downregulated serum malondialdehyde, a marker for oxidative stress and the expression of NFκB and Bcl-2, whereas it upregulated Nrf2, HO-1, and Bax expression at protein level in ovarian tissues. Moreover, genistein intake decreased the activity of mTOR pathway as evidenced by reduced phosphorylation of mTOR, p70S6K1, and 4E-BP1. Taken together, our findings strongly support the potential of genistein in the chemoprevention of ovarian cancer and highlight the effects of the genistein on the molecular pathways involved in ovarian tumorigenesis.

AIMS: Effect of exogenously administered melatonin (N-acetyl 5-methoxytryptamine) on antioxidant systems in experimental Ischemia-Reperfusion (I-R) of rat gastrointestinal system (GIS) was examined. METHODS: A total of 40 rats were divided into 4 groups: Group 1 (Sham), Group 2 (I-R), Group 3 (I-R + 10 mg/kg melatonin) and Group 4 (I-R + 20 mg/kg melatonin). Activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined in small intestines. RESULTS: There was a significant (p<0.05) reduction in GSH-Px levels in Group 2 (64.16+/-7.02 U/mg protein) compared to Group 1 (80.15+/-9.32 U/mg protein). We observed a meaningful increase in GSH-Px levels in melatonin applied groups (Group 3: 75.94+/-9.83 U/mg protein, Group 4: 78.55+/-9.11 U/mg protein) compared to Group 2. Correspondingly, SOD activity levels were significantly reduced (p<0.001) in Group 2 (24.14+/-4.35 U/mg protein) compared to controls (52.91+/-6.13 U/mg protein). A stronger effect (p<0.001) of melatonin was observed on SOD levels compared to GSH-Px levels in both doses (Group 3: 38.96+/-6.39 U/mg protein, Group 4: 43.07+/-7.76 U/mg protein). Levels of selenium were reduced significantly in Group 2 (1.11+/-0.31 microg/g tissue) compared to Group 1 (2.01+/-0.19 microg/g tissue). Melatonin application in Group 3 (1.13+/-0.28 microg/g tissue) and Group 4 (1.89+/-0.48 microg/g tissue) caused an increase in selenium levels. There was a strong correlation between increases in selenium and GSH-Px levels in Group 4 (r:0.651 p<0.01). CONCLUSIONS: Melatonin seems to exert its antioxidant effect in GIS tract by stimulating SOD and GSH-Px. Selenium also seems to have an antioxidant contribution on protecting rat gastrointestinal tract I-R injury.