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Low-dose polystyrene microplastics exposure promotes human prostate cancer cell proliferation via GPX4‑mediated
Jingmo Li1, Chenyao Deng2, Wenyu Zou3
1Research Center, Peking University First Hospital, Beijing 100034, China.
Abstract:
Microplastics are increasingly recognized as potential threats to human health. In our previous study, polystyrene microplastics (PS-MPs) were detected in both para-tumor and tumor tissues of human prostate samples, with significantly higher abundance observed in tumor tissues compared to their paired para-tumor counterparts. However, whether and how PS-MPs contribute to the progression of prostate cancer remains poorly understood. This study aims to investigate the effects and underlying mechanisms of PS-MPs exposure on the proliferation of human prostate cancer cells. To this end, we exposed both the human prostate cancer cell line LNCaP and primary cultured human prostate cancer cells to varying doses of 1-μm-diameter PS-MPs. Our results showed that low-dose (0.1 μg/mL) PS-MPs exposure for 48 significantly promoted the proliferation of LNCaP cells. Additionally, PS-MPs exposure altered the expression of certain inflammatory factors and induced oxidative stress in LNCaP cells. We also observed upregulation of GPX4 and ACSL4 in LNCaP cells and primary prostate cancer cells following PS-MPs exposure. Notably, GPX4 knockdown reversed the effects of PS-MPs on reactive oxygen species (ROS) levels, lipid peroxidation, and glutathione content, likely by promoting ferroptosis. Taken together, our findings highlight a critical role for ferroptosis in PS-MPs-induced proliferation of human prostate cancer cells under low-dose exposure.
Insights
Low-dose polystyrene microplastics (PS-MPs) exposure significantly promoted human prostate cancer cell proliferation. This effect was linked to ferroptosis, a cell death pathway, and increased oxidative stress, highlighting a new health concern.
Area of Science:
- Environmental Health
- Oncology
- Cell Biology
Background:
- Microplastics (MPs), particularly polystyrene microplastics (PS-MPs), are increasingly detected in human tissues, including prostate samples.
- Previous studies found higher PS-MP abundance in prostate tumors than adjacent tissues, but their role in cancer progression is unclear.
Purpose of the Study:
- To investigate the effects of PS-MPs on human prostate cancer cell proliferation.
- To elucidate the underlying mechanisms, including inflammatory responses, oxidative stress, and ferroptosis.
Main Methods:
- Exposure of LNCaP cells and primary prostate cancer cells to varying doses of 1-μm PS-MPs.
- Analysis of cell proliferation, inflammatory factors, oxidative stress markers (ROS, lipid peroxidation, glutathione), and ferroptosis-related genes (GPX4, ACSL4).
- GPX4 knockdown experiments to confirm its role in PS-MP effects.
Main Results:
- Low-dose (0.1 μg/mL) PS-MPs significantly promoted LNCaP cell proliferation.
- PS-MPs exposure induced oxidative stress and altered inflammatory factor expression.
- Upregulation of GPX4 and ACSL4 was observed in PS-MP-exposed cells.
- GPX4 knockdown reversed PS-MP-induced changes in ROS, lipid peroxidation, and glutathione, indicating ferroptosis involvement.
Conclusions:
- Low-dose PS-MPs exposure can enhance human prostate cancer cell proliferation.
- Ferroptosis plays a critical role in PS-MPs-induced cancer cell proliferation.
- These findings underscore the potential health risks of microplastic contamination in the context of cancer progression.
