TY - JOUR
T1 - Curcumin Prevents Epithelial-to Mesenchymal Transition-Mediated OvarianCancerProgressionthroughNRF2/ETBR/ET-1AxisandPreserves Mitochondria Biogenesis in Kidney after Cisplatin Administration
AU - Barinda, Agian Jeffilano
AU - Arozal, Wawaimuli
AU - Sandhiutami, Ni Made Dwi
AU - Louisa, Melva
AU - Arfian, Nur
AU - Sandora, Normalina
AU - Yusuf, Mochammad
N1 - Funding Information:
This research was funded by Direktorat Riset dan Pengabdian Masyarakat (DRPM) Universitas Indonesia, NKB-0241/UN2.R3.1/ HKP.05.00/2019
Publisher Copyright:
© 2022 The Author (s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Cisplatin-induced kidney injury
KW - Curcumin
KW - Endothelin-1
KW - ETBR
KW - NRF2
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85127094179&partnerID=8YFLogxK
U2 - 10.34172/apb.2022.014
DO - 10.34172/apb.2022.014
M3 - Article
AN - SCOPUS:85127094179
SN - 2228-5881
VL - 12
SP - 128
EP - 141
JO - Advanced Pharmaceutical Bulletin
JF - Advanced Pharmaceutical Bulletin
IS - 1
ER -
