Curcumin Prevents Epithelial-to Mesenchymal Transition-Mediated OvarianCancerProgressionthroughNRF2/ETBR/ET-1AxisandPreserves Mitochondria Biogenesis in Kidney after Cisplatin Administration

Abstract

Purpose: Ovarian carcinoma is one of the gynaecological malignancies that have the highest mortality rates due to its progressivity. Endothelin signalling plays a leading role in the progression of ovarian cancer through epithelial-to-mesenchymal transition (EMT). Cisplatin (CIS) commonly used as potent chemotherapy; however, its application hindered by its nephrotoxic 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 antioxidant enzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of CUR on ovarian cancer progression and CIS-induced kidney injury remain unknown. Methods: CUR was used as a supplementary therapy together with CIS in human ovarian cancer cell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in the ovarian cancer rat model after CIS ± CUR administration will also be analyzed Results: Co-treatment of CIS with CUR enhanced the expression of a gene involved in apoptosis in association with nuclear factor erythroid-2-related factor 2 (NRF2) enhancement, thus activated endothelin B (ETBR)-mediated ET-1 clearance in SKOV3 cell and ovarian cancer model in rat. Moreover, CUR treatment improved mitochondria biogenesis markers such as PGC-1α and TFAM and prevented the elevated of ET-1-mediated renal fibrosis and apoptosis in kidney isolated from CIS-treated ovarian cancer rat. Conclusion: CUR could be potentially added as an anticancer adjuvant with protective effects in the kidney; thus, improves the efficacy and safety of CIS treatment in the clinical setting.