Icariin‑curcumol promotes ferroptosis in prostate cancer cells through Nrf2/HO‑1 signaling

Sheng,Wen; Li,Bonan; Sun,Tiansong; Zhu,Congxu; Li,Yingqiu; Xu,Wenjing

doi:10.3892/etm.2024.12519

Icariin‑curcumol promotes ferroptosis in prostate cancer cells through Nrf2/HO‑1 signaling

Authors:
- Wen Sheng
- Bonan Li
- Tiansong Sun
- Congxu Zhu
- Yingqiu Li
- Wenjing Xu
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Affiliations: School of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China, Department of Dermatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410021, P.R. China
Published online on: March 26, 2024 https://doi.org/10.3892/etm.2024.12519
Article Number: 232
Copyright: © Sheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ferroptosis is a form of regulatory cell death that relies on iron and reactive oxygen species (ROS) to inhibit tumors. The present study aimed to investigate whether icariin‑curcumol could be a novel ferroptosis inducer in tumor inhibition. Various concentrations of icariin‑curcumol were used to stimulate prostate cell lines (RWPE‑2, PC‑3, VCAP and DU145). Small interfering negative control (si‑NC) and si‑nuclear factor erythroid 2‑related factor 2 (Nrf2) were used to transfect DU145 cells. Cell viability was determined by using cell counting kit‑8. Ferroptosis‑related factor levels were analyzed using western blotting and reverse transcription‑quantitative PCR. Enzyme‑linked immunosorbent assays were used to assess the ferrous (Fe²⁺), glutathione and malondialdehyde (MDA) content. The ROS fluorescence intensity was assessed using flow cytometry. DU145 cells were most sensitive to icariin‑curcumol concentration. The Fe²⁺ content, ROS fluorescence intensity and MDA level gradually increased, while solute carrier family 7 member 11 (SLC7A11) level, glutathione peroxidase 4 (GPX4) level, GSH content, Nrf2 and heme oxygenase‑1 (HO‑1) decreased with icariin‑curcumol in a dose‑dependent manner. After si‑Nrf2 was transfected, the cell proliferation ability, SLC7A11 and GPX4 levels declined compared with the si‑NC group. In contrast to the control group, the icariin + curcumol group showed reductions in Nrf2 and HO‑1 levels, cell proliferation, SLC7A11 and GPX4 levels, with an increase in Fe²⁺ content and ROS fluorescence intensity. Overexpression of Nrf2 reversed the regulation observed in the icariin + curcumol group. Icariin‑curcumol induced ferroptosis in PCa cells, mechanistically by inhibiting the Nrf2/HO‑1 signaling pathway. Icariin‑curcumol could be used as a new type of ferroptosis inducer to treat PCa effectively.

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