Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding
This study employed computational biology approaches to investigate the interactions between per- and polyfluoroalkyl substances (PFAS) and key colorectal cancer (CRC) proteins. The results indicate that PFAS may influence CRC progression by modulating multiple proteins, particularly glutathione S-t...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325002611 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850051271996735488 |
|---|---|
| author | Jinxiao Li Yanran Wu Pian Ye Dongmei Zuo Shuangjiao Deng Ran Pang Huarong Li |
| author_facet | Jinxiao Li Yanran Wu Pian Ye Dongmei Zuo Shuangjiao Deng Ran Pang Huarong Li |
| author_sort | Jinxiao Li |
| collection | DOAJ |
| description | This study employed computational biology approaches to investigate the interactions between per- and polyfluoroalkyl substances (PFAS) and key colorectal cancer (CRC) proteins. The results indicate that PFAS may influence CRC progression by modulating multiple proteins, particularly glutathione S-transferase A1 (GSTA1). Computational analysis revealed that PFAS 14 exhibits high binding affinity for GSTA1, occupying its glutathione-binding site. Further simulations confirmed the stable binding of PFAS 14 across different environments, forming persistent hydrogen bonds and water bridges, suggesting a potential inhibitory effect on GSTA1.GSTA1, a key member of the glutathione S-transferase family, plays a critical role in detoxification by catalyzing the conjugation of glutathione to electrophilic compounds. Dysregulation of GSTA1 has been implicated in cancer progression and chemoresistance. In CRC, altered GSTA1 expression may affect tumor metabolism and drug response, making it a potential therapeutic target.This study identifies GSTA1 as a key target of PFAS interactions, suggesting that environmental PFAS exposure may influence CRC by interfering with detoxification mechanisms. The competitive inhibition of GSTA1 by PFAS 14 may impact cancer cell survival and progression. Future research should integrate experimental validation to assess its phenotypic effects and evaluate PFAS 14 as a potential GSTA1 inhibitor. |
| format | Article |
| id | doaj-art-d2b2bc76b90f44e9869714ceb4197a85 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-d2b2bc76b90f44e9869714ceb4197a852025-08-20T02:53:12ZengElsevierEcotoxicology and Environmental Safety0147-65132025-03-0129211792510.1016/j.ecoenv.2025.117925Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive bindingJinxiao Li0Yanran Wu1Pian Ye2Dongmei Zuo3Shuangjiao Deng4Ran Pang5Huarong Li6Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan Hubei, 430022, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of infectious diseases，Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan, Hubei 430022, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan, Hubei 430022, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan, Hubei 430022, ChinaDepartment of infectious diseases，Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan, Hubei 430022, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan, Hubei 430022, China; Corresponding author.This study employed computational biology approaches to investigate the interactions between per- and polyfluoroalkyl substances (PFAS) and key colorectal cancer (CRC) proteins. The results indicate that PFAS may influence CRC progression by modulating multiple proteins, particularly glutathione S-transferase A1 (GSTA1). Computational analysis revealed that PFAS 14 exhibits high binding affinity for GSTA1, occupying its glutathione-binding site. Further simulations confirmed the stable binding of PFAS 14 across different environments, forming persistent hydrogen bonds and water bridges, suggesting a potential inhibitory effect on GSTA1.GSTA1, a key member of the glutathione S-transferase family, plays a critical role in detoxification by catalyzing the conjugation of glutathione to electrophilic compounds. Dysregulation of GSTA1 has been implicated in cancer progression and chemoresistance. In CRC, altered GSTA1 expression may affect tumor metabolism and drug response, making it a potential therapeutic target.This study identifies GSTA1 as a key target of PFAS interactions, suggesting that environmental PFAS exposure may influence CRC by interfering with detoxification mechanisms. The competitive inhibition of GSTA1 by PFAS 14 may impact cancer cell survival and progression. Future research should integrate experimental validation to assess its phenotypic effects and evaluate PFAS 14 as a potential GSTA1 inhibitor.http://www.sciencedirect.com/science/article/pii/S0147651325002611PFASColorectal cancerSurvival analysisComputational biologyGSTA1Competitive binding |
| spellingShingle | Jinxiao Li Yanran Wu Pian Ye Dongmei Zuo Shuangjiao Deng Ran Pang Huarong Li Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding Ecotoxicology and Environmental Safety PFAS Colorectal cancer Survival analysis Computational biology GSTA1 Competitive binding |
| title | Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding |
| title_full | Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding |
| title_fullStr | Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding |
| title_full_unstemmed | Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding |
| title_short | Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding |
| title_sort | computational insights into the inhibitory effects of pfas 14 on colorectal cancer targeting gsta1 through competitive binding |
| topic | PFAS Colorectal cancer Survival analysis Computational biology GSTA1 Competitive binding |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325002611 |
| work_keys_str_mv | AT jinxiaoli computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding AT yanranwu computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding AT pianye computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding AT dongmeizuo computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding AT shuangjiaodeng computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding AT ranpang computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding AT huarongli computationalinsightsintotheinhibitoryeffectsofpfas14oncolorectalcancertargetinggsta1throughcompetitivebinding |