Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through
Jinxiao Li1, Yanran Wu2, Pian Ye3
1Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan Hubei, 430022, China.
Abstract:
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.
Insights
Per- and polyfluoroalkyl substances (PFAS) may impact colorectal cancer (CRC) by interacting with key proteins like glutathione S-transferase A1 (GSTA1). PFAS 14 specifically binds to GSTA1, potentially inhibiting its function and affecting cancer progression.
Area of Science:
- Environmental Health
- Computational Biology
- Oncology
Background:
- Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants with potential health implications.
- Glutathione S-transferase A1 (GSTA1) is crucial for detoxification and its dysregulation is linked to colorectal cancer (CRC) progression and chemoresistance.
Purpose of the Study:
- To investigate the molecular interactions between PFAS and key colorectal cancer (CRC) proteins using computational methods.
- To identify specific PFAS compounds and their binding affinities to potential CRC-related protein targets.
Main Methods:
- Employed computational biology approaches, including molecular docking and simulations.
- Analyzed the binding affinity and stability of PFAS compounds with target proteins, focusing on GSTA1.
Main Results:
- PFAS compounds show potential to modulate multiple CRC proteins, with a notable interaction with GSTA1.
- PFAS 14 demonstrated high binding affinity for GSTA1, specifically targeting its glutathione-binding site.
- Simulations confirmed stable binding of PFAS 14 to GSTA1, suggesting a potential inhibitory mechanism.
Conclusions:
- GSTA1 is identified as a key protein target for PFAS interactions in the context of colorectal cancer.
- Environmental PFAS exposure may influence CRC by interfering with GSTA1-mediated detoxification pathways.
- PFAS 14's potential as a competitive inhibitor of GSTA1 warrants further experimental investigation for its effects on cancer cell survival and progression.
