Curcumin Prevents Epithelial-to Mesenchymal Transition-Mediated Ovarian Cancer Progression through NRF2/ETBR/ET-1 Axis and Preserves Mitochondria Biogenesis in Kidney after Cisplatin Administration

Purpose: Ovarian carcinoma is one of the gynaecological malignancies that have the highestmortality rates due to its progressivity. Endothelin signalling plays a leading role in theprogression of ovarian cancer through epithelial-to-mesenchymal transition (EMT). Cisplatin(CIS) commonly used as potent chemotherapy; however, its application hindered by itsnephrotoxic effect. Curcumin (CUR), a turmeric-derived compound, has an anticancer property,as well as a renal protective effect. Moreover, CUR augments the affinity of the antioxidantenzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of CUR on ovarian cancerprogression and CIS-induced kidney injury remain unknown.Methods: CUR was used as a supplementary therapy together with CIS in human ovarian cancercell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in theovarian cancer rat model after CIS ± CUR administration will also be analyzedResults: Co-treatment of CIS with CUR enhanced the expression of a gene involved in apoptosisin association with nuclear factor erythroid-2-related factor 2 (NRF2) enhancement, thusactivated endothelin B (ETBR)-mediated ET-1 clearance in SKOV3 cell and ovarian cancermodel in rat. Moreover, CUR treatment improved mitochondria biogenesis markers such asPGC-1α and TFAM and prevented the elevated of ET-1-mediated renal fibrosis and apoptosis inkidney isolated from CIS-treated ovarian cancer rat.Conclusion: CUR could be potentially added as an anticancer adjuvant with protective effectsin the kidney; thus, improves the efficacy and safety of CIS treatment in the clinical setting.