PMID- 36168316
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220929
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Print)
IS  - 1792-1074 (Linking)
VI  - 24
IP  - 4
DP  - 2022 Oct
TI  - Norcantharidin induces ferroptosis via the suppression of NRF2/HO-1 signaling in 
      ovarian cancer cells.
PG  - 359
LID - 10.3892/ol.2022.13479 [doi]
LID - 359
AB  - Increasing evidence has indicated a crucial role of ferroptosis in ovarian cancer 
      (OC). Norcantharidin (NCTD), a normethyl compound of cantharidin, is extensively 
      used in clinical practice as an optional anticancer drug. However, whether NCTD 
      leads to ferroptosis in OC has not been previously explored, at least to the best 
      of our knowledge. In the present study, the effect of NCTD on SKOV3 and OVCAR-3 
      cells was evaluated. The experimental data of the present study revealed that 
      NCTD significantly suppressed SKOV3 and OVCAR-3 cell viability in a 
      concentration- and time-dependent manner. The results of Cell Counting Kit-8 
      assay revealed that NCTD treatment decreased SKOV3 and OVCAR-3 cell viability. In 
      comparison, pre-incubation with ferrostatin-1 (Fer-1) significantly reversed the 
      NCTD-induced reduction in SKOV3 and OVCAR-3 cell viability; however, no changes 
      in cell viability were observed when the SKOV3 and OVCAR-3 cells were treated 
      with NCTD, in combination with the apoptosis inhibitor, Z-VAD-FMK, the 
      ferroptosis inhibitor, necrostatin-1, and the autophagy inhibitor, 
      3-methyladenine. Additionally, it was observed that NCTD markedly enhanced 
      reactive oxygen species production and malondialdehyde and ferrous ion levels in 
      the SKOV3 and OVCAR-3 cells; however, pre-incubation with Fer-1 abolished these 
      effects. Flow cytometry also demonstrated a significant increase in cell death 
      following treatment of the SKOV3 and OVCAR-3 cells with NCTD; however, 
      pre-incubation with Fer-1 also reversed these effects. In vivo experiments 
      demonstrated that NCTD significantly reduced tumor volume and weight. More 
      importantly, it was revealed that nuclear factor erythroid 2-related factor 2 
      (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute 
      carrier family 7 member 11 (xCT) expression levels were significantly decreased 
      following NCTD treatment. Collectively, NCTD may represent a potent anticancer 
      agent in OC cells, and NCTD-induced ferroptotic cell death may be achieved by 
      inhibiting the NRF2/HO-1/GPX4/xCT axis.
CI  - Copyright: (c) Zhu et al.
FAU - Zhu, Xiaoyan
AU  - Zhu X
AD  - Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong 
      University, Yancheng, Jiangsu 224700, P.R. China.
FAU - Chen, Xiaohong
AU  - Chen X
AD  - Department of Gynecology, People's Hospital of Gansu Province, Lanzhou, Gansu 
      730000, P.R. China.
FAU - Qiu, Longshan
AU  - Qiu L
AD  - Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong 
      University, Yancheng, Jiangsu 224700, P.R. China.
FAU - Zhu, Jianhua
AU  - Zhu J
AD  - Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong 
      University, Yancheng, Jiangsu 224700, P.R. China.
FAU - Wang, Jiancai
AU  - Wang J
AD  - Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong 
      University, Yancheng, Jiangsu 224700, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20220825
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC9478624
OTO - NOTNLM
OT  - ferroptosis
OT  - norcantharidin
OT  - nuclear factor erythroid 2-related factor 2
OT  - ovarian cancer
COIS- The authors declare that they have no competing interests.
EDAT- 2022/09/29 06:00
MHDA- 2022/09/29 06:01
PMCR- 2022/08/25
CRDT- 2022/09/28 01:53
PHST- 2022/01/07 00:00 [received]
PHST- 2022/05/19 00:00 [accepted]
PHST- 2022/09/28 01:53 [entrez]
PHST- 2022/09/29 06:00 [pubmed]
PHST- 2022/09/29 06:01 [medline]
PHST- 2022/08/25 00:00 [pmc-release]
AID - OL-24-04-13479 [pii]
AID - 10.3892/ol.2022.13479 [doi]
PST - epublish
SO  - Oncol Lett. 2022 Aug 25;24(4):359. doi: 10.3892/ol.2022.13479. eCollection 2022 
      Oct.