Role of Oxidative Stress in Prognosis of Ovarian Cancer.

Ovarian cancer is one of the most lethal gynecological malignancies. Mitochondria are the predominant source of reactive oxygen species (ROS) in the cell. Besides mitochondria nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) enzymes generate a significant amount of ROS in the cell. The present work establishes an interesting link between NOX4 enzyme (which is an important source of reactive oxygen species "ROS") and PHB1 (as a holdase type chaperone in mitochondrial stress). The current study was conducted on 60 patients with ovarian tumours (benign, borderline and malignant) and 20 healthy volunteers (as a control group). NOX4 expression was assessed by TaqMan® real time gene expression assay, while cellular expression of prohibitin was evaluated by immunohistochemistry. There was a significant increase in prohibitin expression from benign cystadenoma to malignant tumors. In addition, there was an increase in NOX4 expression. In conclusion, over-expression of PHB1 and NOX4 in malignant ovarian tissues suggest that PHB1 is associated with tumorigenesis via activation of NOX4 enzyme with subsequent release of ROS in the cells.

Prohibitin: targeting peptide coupled to ovarian cancer, luteinization and TGF-ß pathways.

BACKGROUND: Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-ß has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-ß and LH in ovarian cancer. METHODS: The study was conducted on 60 patients with ovarian tumors (benign, borderline and malignant) and 20 healthy volunteers. LH and TGF-ß serum levels were measured by ELISA. Expression of prohibitin and LHR-mRNA were assessed by IHC and TaqMan® real time gene expression assay, respectively. RESULTS: Serum levels of LH and TGF-ß were significantly decreased among borderline and malignant groups. There was significant over-expression of LHRmRNA in malignant group. Prohibitin expression was significantly increased in malignant ovarian tissue. Strong negative correlations were found between LHR mRNA expression and serum LH levels, and between IHC score of prohibitin and serum levels of LH among patients with borderline ovarian tumors. CONCLUSION: Steady decline of LH and TGF-B serum levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their inhibitory role against OET cell growth. Increased PHB1 expression in OET suggests its proliferative activity that can be regulated by luteinisation and/or TGF-ß. Furthermore increased LHR mRNA tissue expression can provide hope for using LH in treatment of some types of ovarian cancers.