The investigation of plant secondary metabolites effects on metabolism of eukoryatic models

Epithelial ovarian cancer (EOC) is the fourth or fifth most common cause of death from all cancers among women. As the disease is asymptomatic at late detection, the tumor has metastasized at the time of diagnosis and after surgery it recurrences within 16–22 months with the development of a chemoresistant disease. Approximately 90 percent of primary malignant ovarian tumors are epithelial (carcinomas). Recent studies focus on the mechanism of initiation and progression of carcinoma by investigating the role played by cell-cell adhesion during the transformation of epithelial cells. In general, this thesis focused on two main goals, which mechanism(s) cause to ovarian cancer progression and whether phytochemicals can be used for the treatment. We first investigated whether or which of claudins, tetraspanins, and nontraditional cell adhesion molecule, EpCAM are located in tetraspanin-enriched microdomains and by which PKC isoform regulate these possible interactions. The results showed that EpCAM-claudin-4/7 interactions were responsible for the ovarian cancer progression. These interactions were characterized with the further studies. Also, claudins in these interactions were phosphorylated by PKC delta or eta, showing phosphorylation modulates the complex formation, membrane localization, and stability. There is an urgent need to find some safer cancer therapeutic and preventive agents, due to unexpected adverse side-effects of using chemotherapeutic drugs. Epidemiological studies have suggested that specific dietary consumption patterns are associated with risk of developing cancer. Targets for chemoprevention of phytochemicals, especially flavonoids may be multiple including induced antioxidant system, apoptosis or autophagy, and cell cycle arrest. We tested the effects of apigenin, myricetin, and luteolin on the ROS production, apoptosis, autophagy and cell cycle as well as the cell adhesion. These flavonoids affected ovarian cancer progression mechanism depending on the flavonoid type and concentration. The results directed flavonoids may be used to block, retard, or reverse the development and progression of ovarian carcinogenesis.