Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway

Haiying ZHAO; Jianrong LIU; Yang XIANG

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Haiying ZHAO, Jianrong LIU, Yang XIANG. Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway[J]. Journal of Kunming Medical University.

Citation:

Haiying ZHAO, Jianrong LIU, Yang XIANG. Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway[J]. Journal of Kunming Medical University.

Haiying ZHAO, Jianrong LIU, Yang XIANG. Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway[J]. Journal of Kunming Medical University.

Citation:

Haiying ZHAO, Jianrong LIU, Yang XIANG. Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway[J]. Journal of Kunming Medical University.

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Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway

1.
Department of Urology，The 961st Hospital of the Joint Service Support Force of the People’s Liberation Army of China，Qiqihar Heilongjiang 161000
2.
Department of Urology，Qiqihar First Hospital，Qiqihar Heilongjiang 161000，China

Received Date: 2025-07-02
Available Online: 2026-03-29

Abstract

Abstract

Purpose To investigate whether erianin induces ferroptosis in prostate cancer cells by regulating the Keap1/Nrf2/HO-1 signaling pathway, and to elucidate its potential molecular mechanisms. Methods Human prostate cancer cell lines DU145 and PC-3 were cultured. Cell viability was detected by CCK-8 assay, cell proliferation by colony formation assay, cell invasion by Transwell assay, and cell apoptosis by flow cytometry. Intracellular reactive oxygen species （ROS） content was analyzed using the ROS-specific probe DCFH-DA, and the levels of malondialdehyde （MDA） and glutathione （GSH） were determined. Western blot was used to detect the expression of metastatic phenotypic markers （vimentin, N-cadherin, slug, snail, and MMP-9）, ferroptosis-negative regulatory proteins （GPX4, CHAC2, SLC40A1, SLC7A11, and glutaminase）, and proteins related to the Keap1/Nrf2/HO-1 signaling pathway. Results Compared with the control group, erianin significantly reduced the viability of prostate cancer cells （DU145, PC-3） and inhibited their proliferation, migration, and invasion abilities （P < 0.05）. Erianin inhibited the migration of prostate cancer cells by downregulating the mesenchymal markers （vimentin, N-cadherin, slug, snail, and MMP-9） and upregulating the epithelial marker E-cadherin. ROS accumulation, GSH depletion, and lipid peroxidation were significantly increased. Erianin-induced prostate cancer cell death could be rescued by co-treatment with the ROS inhibitor N-acetyl-L-cysteine （NAC） and glutathione （GSH）. After erianin treatment, the proportion of Phen Green SK-positive cells （detecting intracellular free Fe²⁺） was significantly decreased （P < 0.05）. Transmission electron microscopy （TEM） revealed mitochondrial matrix condensation and cristae enlargement in erianin-treated prostate cancer cells. Additionally, erianin treatment significantly downregulated the expression of ferroptosis-negative regulatory proteins （GPX4, CHAC2, SLC40A1, SLC7A11, and glutaminase）. Co-treatment with ferroptosis inhibitors （Liproxstatin-1, Lip-1; or Ferrostatin-1, Fer-1） blocked erianin-induced prostate cancer cell death. Erianin increased Keap1 protein expression while decreasing the expression of Nrf2, HO-1, and NQO1 proteins in cells. CPUY192018 enhanced ferroptosis in prostate cancer cells, indicating that erianin induces ferroptosis through targeting the Keap1/Nrf2/HO-1 signaling pathway. Conclusion: Erianin induces cell death and suppresses prostate cancer cell migration by targeting the Keap1/Nrf2/HO-1 signaling pathway.
- Erianin,
- Keap1/Nrf2/HO-1 Signaling pathway,
- Prostate cancer,
- Ferroptosis

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References(17)

References

[1]	Vietri M T, D’Elia G, Caliendo G, et al. Hereditary prostate cancer: Genes related, target therapy and prevention[J]. Int J Mol Sci, 2021, 22(7): 3753. doi: 10.3390/ijms22073753
[2]	Rosellini M, Santoni M, Mollica V, et al. Treating prostate cancer by antibody-drug conjugates[J]. Int J Mol Sci, 2021, 22(4): 1551. doi: 10.3390/ijms22041551
[3]	Ghafouri-Fard S, Shabestari F A, Vaezi S, et al. Emerging impact of quercetin in the treatment of prostate cancer[J]. Biomed Pharmacother, 2021, 138: 111548. doi: 10.1016/j.biopha.2021.111548
[4]	Zhang Y, Zhang Q, Wei F, et al. Progressive study of effects of erianin on anticancer activity[J]. Onco Targets Ther, 2019, 12: 5457-5465.
[5]	Liu Y T, Hsieh M J, Lin J T, et al. Erianin induces cell apoptosis through ERK pathway in human nasopharyngeal carcinoma[J]. Biomed Pharmacother, 2019, 111: 262-269. doi: 10.1016/j.biopha.2018.12.081
[6]	Rhea L P, Mendez-Marti S, Kim D, et al. Role of immunotherapy in bladder cancer[J]. Cancer Treat Res Commun, 2021, 26: 100296. doi: 10.1002/1097-0142(19870615)59:12<2027::aid-cncr2820591210>3.0.co;2-n
[7]	董建设, 赵俊峰, 张林超, 等. 毛兰素通过调控lncRNA LINC01354/miR-515-5p对前列腺癌细胞糖酵解、增殖、迁移和侵袭的影响[J]. 中成药, 2022, 44(8): 2688-2693. doi: 10.3969/j.issn.1001-1528.2022.08.050
[8]	Xiang Y, Chen X, Wang W, et al. Natural product erianin inhibits bladder cancer cell growth by inducing ferroptosis via NRF2 inactivation[J]. Front Pharmacol, 2021, 12: 775506. doi: 10.3389/fphar.2021.775506
[9]	Li J, Xiong C, Xu P, et al. Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway[J]. Bioengineered, 2021, 12(1): 402-413. doi: 10.1080/21655979.2020.1868733
[10]	Luo Q, Li X, Gan G, et al. PPT1 reduction contributes to erianin-induced growth inhibition in oral squamous carcinoma cells[J]. Front Cell Dev Biol, 2021, 9: 764263. doi: 10.3389/fcell.2021.764263
[11]	Fu Y, Sui B, Xiang L, et al. Emerging understanding of apoptosis in mediating mesenchymal stem cell therapy[J]. Cell Death Dis, 2021, 12(6): 596. doi: 10.1038/s41419-021-03883-6
[12]	Park E, Chung S W. ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation[J]. Cell Death Dis, 2019, 10(11): 822. doi: 10.1038/s41419-019-2064-5
[13]	Kong Y, Akatsuka S, Motooka Y, et al. BRCA1 haploinsufficiency promotes chromosomal amplification under Fenton reaction-based carcinogenesis through ferroptosis-resistance[J]. Redox Biol, 2022, 54: 102356. doi: 10.1016/j.redox.2022.102356
[14]	Baird L, Yamamoto M. The molecular mechanisms regulating the KEAP1-NRF2 pathway[J]. Mol Cell Biol, 2020, 40(13): e00099.
[15]	Li J, Lu K, Sun F, et al. Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway[J]. J Transl Med, 2021, 19(1): 96. doi: 10.1186/s12967-021-02745-1
[16]	Hassanein E H M, Sayed A M, Hussein O E, et al. Coumarins as modulators of the Keap1/Nrf2/ARE signaling pathway[J]. Oxid Med Cell Longev, 2020, 2020: 1675957. doi: 10.1155/2020/1675957
[17]	Jiang G, Liang X, Huang Y, et al. p62 promotes proliferation, apoptosis-resistance and invasion of prostate cancer cells through the Keap1/Nrf2/ARE axis[J]. Oncol Rep, 2020, 43(5): 1547-1557. doi: 10.3892/or.2020.7527

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