Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models
Bisphenol A (BPA), an endocrine disruptor, is linked to cancer progression in estrogen-responsive tissues, but its role in promoting colorectal cancer (CRC) progression in the context of obesity remains underexplored. This study examines BPA's influence on CRC in obese Sprague-Dawley rats using...
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| Format: | Article |
| Language: | English |
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Academic Press
2025
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| Online Access: | http://psasir.upm.edu.my/id/eprint/115882/ http://psasir.upm.edu.my/id/eprint/115882/1/115882.pdf |
| _version_ | 1848866881361936384 |
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| author | Saad, Muhamad Fikri Shazlan Abdullah, Muhammad Nazrul Hakim Lim, Vuanghao Bahari, Hasnah Khoo, Boon Yin Tan, Jun Jie Yong, Yoke Keong |
| author_facet | Saad, Muhamad Fikri Shazlan Abdullah, Muhammad Nazrul Hakim Lim, Vuanghao Bahari, Hasnah Khoo, Boon Yin Tan, Jun Jie Yong, Yoke Keong |
| author_sort | Saad, Muhamad Fikri Shazlan |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Bisphenol A (BPA), an endocrine disruptor, is linked to cancer progression in estrogen-responsive tissues, but its role in promoting colorectal cancer (CRC) progression in the context of obesity remains underexplored. This study examines BPA's influence on CRC in obese Sprague-Dawley rats using network toxicology and experimental models. Computational analysis using the Database for Annotation, Visualization, and Integrated Discovery identified pathways such as “CRC” and “chemical carcinogenesis-receptor activation”, implicating the PI3K-AKT pathway in IL-1 beta upregulation and BPA's role in CRC during obesity. Thirty male rats were grouped (n = 6) as follows: N (normal diet), NC (normal diet + CRC), HC (high-fat diet + CRC), NCB (normal diet + CRC + BPA), and HCB (high-fat diet + CRC + BPA). CRC was induced with 1,2-dimethylhydrazine (40 mg/kg), and BPA (25 mg/kg) was administered for 19 weeks. Although BPA exposure did not affect body weight or biochemical parameters, the HCB group exhibited significant histopathological changes in the colon, including lymphoid hyperplasia, liver damage, and increased IL-1β levels. Furthermore, diet influenced adipocyte size, exacerbating BPA's effects on CRC progression. Findings suggest BPA may worsen CRC progression in obese rats through identified pathways, promoting multi-organ pathology and underscoring the need for stricter regulations, especially for vulnerable populations. |
| first_indexed | 2025-11-15T14:27:39Z |
| format | Article |
| id | upm-115882 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:27:39Z |
| publishDate | 2025 |
| publisher | Academic Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1158822025-03-14T01:04:27Z http://psasir.upm.edu.my/id/eprint/115882/ Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models Saad, Muhamad Fikri Shazlan Abdullah, Muhammad Nazrul Hakim Lim, Vuanghao Bahari, Hasnah Khoo, Boon Yin Tan, Jun Jie Yong, Yoke Keong Bisphenol A (BPA), an endocrine disruptor, is linked to cancer progression in estrogen-responsive tissues, but its role in promoting colorectal cancer (CRC) progression in the context of obesity remains underexplored. This study examines BPA's influence on CRC in obese Sprague-Dawley rats using network toxicology and experimental models. Computational analysis using the Database for Annotation, Visualization, and Integrated Discovery identified pathways such as “CRC” and “chemical carcinogenesis-receptor activation”, implicating the PI3K-AKT pathway in IL-1 beta upregulation and BPA's role in CRC during obesity. Thirty male rats were grouped (n = 6) as follows: N (normal diet), NC (normal diet + CRC), HC (high-fat diet + CRC), NCB (normal diet + CRC + BPA), and HCB (high-fat diet + CRC + BPA). CRC was induced with 1,2-dimethylhydrazine (40 mg/kg), and BPA (25 mg/kg) was administered for 19 weeks. Although BPA exposure did not affect body weight or biochemical parameters, the HCB group exhibited significant histopathological changes in the colon, including lymphoid hyperplasia, liver damage, and increased IL-1β levels. Furthermore, diet influenced adipocyte size, exacerbating BPA's effects on CRC progression. Findings suggest BPA may worsen CRC progression in obese rats through identified pathways, promoting multi-organ pathology and underscoring the need for stricter regulations, especially for vulnerable populations. Academic Press 2025 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/115882/1/115882.pdf Saad, Muhamad Fikri Shazlan and Abdullah, Muhammad Nazrul Hakim and Lim, Vuanghao and Bahari, Hasnah and Khoo, Boon Yin and Tan, Jun Jie and Yong, Yoke Keong (2025) Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models. Toxicology and Applied Pharmacology, 495. art. no. 117227. pp. 1-14. ISSN 0041-008X; eISSN: 1096-0333 https://www.sciencedirect.com/science/article/pii/S0041008X25000031 10.1016/j.taap.2025.117227 |
| spellingShingle | Saad, Muhamad Fikri Shazlan Abdullah, Muhammad Nazrul Hakim Lim, Vuanghao Bahari, Hasnah Khoo, Boon Yin Tan, Jun Jie Yong, Yoke Keong Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| title | Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| title_full | Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| title_fullStr | Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| title_full_unstemmed | Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| title_short | Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| title_sort | exploring the role of bisphenol a in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models |
| url | http://psasir.upm.edu.my/id/eprint/115882/ http://psasir.upm.edu.my/id/eprint/115882/ http://psasir.upm.edu.my/id/eprint/115882/ http://psasir.upm.edu.my/id/eprint/115882/1/115882.pdf |