• Ovarian carcinoma
• platinum drugs
• GSH
• cysteine
• xCT/SLC7A11
• NRF2
• SeChry

Ovarian cancer is the main cause of death among gynaecologic diseases and the most wide-spread malignancy in women over 40 years of age after breast cancer. The causes of that situa-tion are substantially three: the histological and molecular heterogeneity; the late diagnosis and detection and finally chemoresistance. Epithelial ovarian cancer, called carcinomas, is the most common (85-90%) and comprehend two different histotypes based on their type of chemoresistance: ovarian serous carcinoma (OSC) characterized by an acquired chemo-resistance and ovarian clear cell carcinoma (OCCC) that shows an intrinsic form of chemo-resistance. Considering that chemoresistance is the reduction of the efficiency of chemotherapy and that glutathione (GSH) is able to nick platinum-based drug effectiveness, the main role of GSH and cysteine (rate-limiting substrate for GSH synthesis), in ovarian cancer, was hypothe-sized. Since the main role of xCT/SLC7A11 in cyst(e)ine transport, we decided to investigate the role of that protein in ovarian cancer chemoresistance using three ovarian cancer cell lines (ES2, OVCAR3 and OVCAR8), upon exposure to cysteine and cisplatin. Therefore, sustaining the idea that NF E2 Relator Factor 2 (NRF2) was able to regulate the xCT/SLC7A11 transcription (in stressful conditions) by binding ARE enhancer sequence in xCT/SLC7A11 promoter, the cells were exposed to Selenium-containing Chrysin (SeChry) that was reported to largely impact xCT expression. Our results, confirmed the role of cysteine in the protection against the damages caused by platinum drugs and the role of xCT in the transport of cysteine, enhancing chemo-resistance.
Concerning SeChry impacts NRF2 binding xCT/SLC7A11 promoter, the results preliminarily showed that NRF2 has a role in xCT/SLC7A11 expression in OVCAR3 cells exposed to SeChry.

The results of that thesis have contributed to publish an article on Nutrients: “Targeting Gluta-thione and Cystathione β-Synthase in Ovarian Cancer Treatment by Selenium-Chrysin Polyurea Dendrimer Nanoformulation”.