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Adv Pharm Bull. 2022;12(1): 128-141.
doi: 10.34172/apb.2022.014
PMID: 35517894
PMCID: PMC9012927
Scopus ID: 85127094179
  Abstract View: 1665
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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 1,2 ORCID logo, Wawaimuli Arozal 1* ORCID logo, Ni Made Dwi Sandhiutami 3,4, Melva Louisa 1 ORCID logo, Nur Arfian 5 ORCID logo, Normalina Sandora 6, Muhammad Yusuf 7

1 Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
2 Metabolic, Cardiovascular and Aging Cluster, Indonesian Medical Education and Research Institute (IMERI), Universitas Indonesia, Jakarta, Indonesia.
3 Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
4 Faculty of Pharmacy, University of Pancasila, Jakarta, Indonesia.
5 Department of Anatomy,Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
6 Human Reproduction, Infertility, and Family Planning Cluster, Indonesian Medical Education and Research Institute (IMERI), Universitas Indonesia, Jakarta, Indonesia.
7 Dharmais Hospital National Cancer Center, Jakarta, Indonesia.
*Corresponding Author: Wawaimuli Arozal, Tel.: +62-21-31930481; Fax: +62-21-3920947, Email: wawaimuli.arozal@ui.ac.id, Email: wawaimuli.arozal@ui.ac.id

Abstract

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.
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Submitted: 07 Apr 2020
Revision: 18 Aug 2020
Accepted: 19 Sep 2020
ePublished: 19 Sep 2020
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