Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage
Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted the detrimental effects of NPs on the digestive tract. However, no studies have reported an association between NPs exposure and colitis-associated cancer (CAC). An azoxymethane/dex...
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Elsevier
2025-01-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412025000091 |
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| author | Shan Tian Ruixue Li Jiao Li Jinhui Zou |
| author_facet | Shan Tian Ruixue Li Jiao Li Jinhui Zou |
| author_sort | Shan Tian |
| collection | DOAJ |
| description | Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted the detrimental effects of NPs on the digestive tract. However, no studies have reported an association between NPs exposure and colitis-associated cancer (CAC). An azoxymethane/dextran sodium sulfate-induced CAC model was used, and polystyrene nanoparticles (PS-NPs) were selected for long-term exposure. Non-targeted metabolomics and 16S rRNA sequencing were used to detect changes in colonic metabolites and gut microbes following PS-NPs exposure. A lipopolysaccharide (LPS)-treated cancer cell model (Caco-2) exposed to PS-NPs was used to investigate the underlying molecular mechanism. Compared to the normal control group, mice in the PS-NPs group exhibited more tumor nodes and reactive oxygen species (ROS), higher expression of pan-CK and Ki-67, and more severe DNA damage. 16S rRNA sequencing revealed that exposure to PS-NPs altered the abundance of Allobaculum and Lactobacillus, whereas metabolic analysis showed that the most significant metabolites were enriched mostly in fatty acid metabolism. Experiments in LPS intervened Caco-2 cells showed that exposure to PS-NPs led to lipid peroxidation, oxidative stress, and DNA damage in Caco-2. Exposure to PS-NPs activated the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway both in the AOM/DSS mouse model and cellular model. Key proteins involved in fatty acid metabolism were downregulated in Caco-2 cells exposed to PS-NPs. The metabolic effects of cancer cells exposed to PS-NPs were significantly inhibited by the activation of the fatty acid metabolism pathway by fenofibrate. PS-NPs exposure disturbed lipid metabolism and induced DNA damage via the activation of PI3K/AKT/mTOR to promote CAC progression. Inhibition of fatty acid metabolism is a therapeutic target for controlling PS-NP-induced CAC. Our study provides an important reference for the prevention and treatment of CAC from the perspective of the environment and enhances awareness of the necessity of plastic control. |
| format | Article |
| id | doaj-art-74ed4b3e105a4b6c8f218d9c3f4a8cde |
| institution | Kabale University |
| issn | 0160-4120 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj-art-74ed4b3e105a4b6c8f218d9c3f4a8cde2025-01-24T04:44:16ZengElsevierEnvironment International0160-41202025-01-01195109258Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damageShan Tian0Ruixue Li1Jiao Li2Jinhui Zou3Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China; Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei, ChinaDepartment of Internal Medicine, The hospital of Wuhan University, Wuhan 430060, Hubei, ChinaDepartment of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China; Corresponding authors.Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei, China; Corresponding authors.Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted the detrimental effects of NPs on the digestive tract. However, no studies have reported an association between NPs exposure and colitis-associated cancer (CAC). An azoxymethane/dextran sodium sulfate-induced CAC model was used, and polystyrene nanoparticles (PS-NPs) were selected for long-term exposure. Non-targeted metabolomics and 16S rRNA sequencing were used to detect changes in colonic metabolites and gut microbes following PS-NPs exposure. A lipopolysaccharide (LPS)-treated cancer cell model (Caco-2) exposed to PS-NPs was used to investigate the underlying molecular mechanism. Compared to the normal control group, mice in the PS-NPs group exhibited more tumor nodes and reactive oxygen species (ROS), higher expression of pan-CK and Ki-67, and more severe DNA damage. 16S rRNA sequencing revealed that exposure to PS-NPs altered the abundance of Allobaculum and Lactobacillus, whereas metabolic analysis showed that the most significant metabolites were enriched mostly in fatty acid metabolism. Experiments in LPS intervened Caco-2 cells showed that exposure to PS-NPs led to lipid peroxidation, oxidative stress, and DNA damage in Caco-2. Exposure to PS-NPs activated the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway both in the AOM/DSS mouse model and cellular model. Key proteins involved in fatty acid metabolism were downregulated in Caco-2 cells exposed to PS-NPs. The metabolic effects of cancer cells exposed to PS-NPs were significantly inhibited by the activation of the fatty acid metabolism pathway by fenofibrate. PS-NPs exposure disturbed lipid metabolism and induced DNA damage via the activation of PI3K/AKT/mTOR to promote CAC progression. Inhibition of fatty acid metabolism is a therapeutic target for controlling PS-NP-induced CAC. Our study provides an important reference for the prevention and treatment of CAC from the perspective of the environment and enhances awareness of the necessity of plastic control.http://www.sciencedirect.com/science/article/pii/S0160412025000091NanoplasticsColitis-associated cancerLipid metabolismGut microbesUlcerative colitis |
| spellingShingle | Shan Tian Ruixue Li Jiao Li Jinhui Zou Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage Environment International Nanoplastics Colitis-associated cancer Lipid metabolism Gut microbes Ulcerative colitis |
| title | Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage |
| title_full | Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage |
| title_fullStr | Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage |
| title_full_unstemmed | Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage |
| title_short | Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage |
| title_sort | polystyrene nanoplastics promote colitis associated cancer by disrupting lipid metabolism and inducing dna damage |
| topic | Nanoplastics Colitis-associated cancer Lipid metabolism Gut microbes Ulcerative colitis |
| url | http://www.sciencedirect.com/science/article/pii/S0160412025000091 |
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