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Lycopene mitigates DHT-induced apoptosis and oxidative stress in human granulosa cell line KGN by regulating the Nrf2 pathway

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Abstract

Background

Recently, accumulating evidence has proved that apoptosis and oxidative stress exert essential roles in the development of polycystic ovarian syndrome (PCOS). Besides, multiple natural products have been identified to be related to the PCOS process.

Objective

This investigation aimed to elucidate the effects and mechanisms of lycopene on granulosa-like tumor cell line (KGN) in the presence of dihydrotestosterone (DHT). KGN cells were treated using DHT or lycopene and cell survival rate was tested by cell counting kit 8 (CCK-8) assay. Also, flow cytometry, western blot as well as enzyme-linked immunosorbent assay (ELISA) were utilized to detect cell apoptosis, protein level and the marker of oxidative stress. ROS accumulation was observed with DCFH-DA dye. The nuclear factor-erythroid 2-related factor (Nrf2) expression in KGN cells was reduced via small interfering RNA (siRNA). The nuclear translocation of Nrf2 was determined through immunofluorescence (IF) analysis.

Results

Lycopene effectively reversed DHT-induced apoptosis in addition to oxidative stress in KGN cells. Besides, lycopene treatment obviously activated Nrf2 signaling and accelerated nuclear translocation of Nrf2 in KGN cells. Nrf2 depletion partially counteracted the role of lycopene in DHT-mediated apoptosis as well as oxidative stress in KGN cells.

Conclusion

In summary, this work revealed that lycopene alleviates oxidative stress and apoptosis in KGN cells in the presence of DHT, which at least partly by depending on the activation of Nrf2 cascade signal at the molecular level.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Gynecology Department, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116000, Liaoning, China

    Yue Chen, Mengmeng Zhao, Xiaoqing Li, Yuanyuan Liu & Yuhong Shang

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  1. Yue Chen
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  2. Mengmeng Zhao
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  3. Xiaoqing Li
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  4. Yuanyuan Liu
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  5. Yuhong Shang
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Contributions

YC and YS conceived the study and designed the experiments. MZ, XL and YL contributed to the data collection, performed the data analysis and interpreted the results. YC wrote the manuscript. YS contributed to the critical revision of article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuhong Shang.

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Author Yue Chen declares that he has no conflict of interest. Author Mengmeng Zhao declares that he has no conflict of interest. Author Xiaoqing Li declares that he has no conflict of interest. Author Yuanyuan Liu declares that he has no conflict of interest. Author Yuhong Shang declares that he has no conflict of interest.

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Chen, Y., Zhao, M., Li, X. et al. Lycopene mitigates DHT-induced apoptosis and oxidative stress in human granulosa cell line KGN by regulating the Nrf2 pathway. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-023-00419-1

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