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Research Article

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

Agian Jeffilano Barinda ORCID logo, Wawaimuli Arozal* ORCID logo, Ni Made Dwi Sandhiutami, Melva Louisa ORCID logo, Nur Arfian ORCID logo, Normalina Sandora, Muhammad Yusuf

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 commonly used as potent chemotherapy; however, its application hindered by its nephrotoxic effect. Curcumin, a turmeric-derived compound, has an anticancer property, as well as a renal protective effect. Moreover, curcumin augments the affinity of the antioxidant enzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of curcumin on ovarian cancer progression and cisplatin-induced kidney injury remain unknown.

Method: Curcumin was used as a supplementary therapy together with cisplatin in Human Ovarian Cancer Cell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in the ovarian cancer rat model after cisplatin ± curcumin administration will also be analyzed

Result: Co-treatment of cisplatin with curcumin enhanced the expression of a gene involved in apoptosis in association with NRF2 enhancement, thus activated ETBR-mediated ET-1 clearance in SKOV3 cell and ovarian cancer model in rat. Moreover, curcumin 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 cisplatin-treated ovarian cancer rat.

Conclusion: Curcumin could be potentially added as an anticancer adjuvant with protective effects in the kidney; thus, improves the efficacy and safety of cisplatin treatment in the clinical setting.

Keywords: Ovarian Cancer, Curcumin, Endothelin-1, NRF2, Cisplatin-induced kidney injury, ETBR
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Submitted: 07 Apr 2020
Revision: 18 Aug 2020
Accepted: 19 Sep 2020
ePublished: 19 Sep 2020
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