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Article Open Access

Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells

Retraction in: /10.3892/ol.2025.14861
  • Authors:
    • Xiaoyan Zhu
    • Xiaohong Chen
    • Longshan Qiu
    • Jianhua Zhu
    • Jiancai Wang
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong University, Yancheng, Jiangsu 224700, P.R. China, Department of Gynecology, People's Hospital of Gansu Province, Lanzhou, Gansu 730000, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 359
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    Published online on: August 25, 2022
       https://doi.org/10.3892/ol.2022.13479
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu X, Chen X, Qiu L, Zhu J and Wang J: Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861. Oncol Lett 24: 359, 2022.
APA
Zhu, X., Chen, X., Qiu, L., Zhu, J., & Wang, J. (2022). Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861. Oncology Letters, 24, 359. https://doi.org/10.3892/ol.2022.13479
MLA
Zhu, X., Chen, X., Qiu, L., Zhu, J., Wang, J."Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861". Oncology Letters 24.4 (2022): 359.
Chicago
Zhu, X., Chen, X., Qiu, L., Zhu, J., Wang, J."Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861". Oncology Letters 24, no. 4 (2022): 359. https://doi.org/10.3892/ol.2022.13479
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu X, Chen X, Qiu L, Zhu J and Wang J: Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861. Oncol Lett 24: 359, 2022.
APA
Zhu, X., Chen, X., Qiu, L., Zhu, J., & Wang, J. (2022). Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861. Oncology Letters, 24, 359. https://doi.org/10.3892/ol.2022.13479
MLA
Zhu, X., Chen, X., Qiu, L., Zhu, J., Wang, J."Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861". Oncology Letters 24.4 (2022): 359.
Chicago
Zhu, X., Chen, X., Qiu, L., Zhu, J., Wang, J."Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells Retraction in /10.3892/ol.2025.14861". Oncology Letters 24, no. 4 (2022): 359. https://doi.org/10.3892/ol.2022.13479
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