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Published on: July 28, 2010
Gut Microbial Metabolite 4-Ethylphenylsulfate Is Selectively Deleterious and Anticancer to Colon Cancer Cells
Jyoti Jaiswal1, Amit Kumar Srivastav2, Manish Kushwaha1,3
1Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India.
Abstract:
Gut microbiota-derived metabolites have emerged as promising candidates in cancer therapeutics. Among these metabolites, 4-ethylphenyl sulfate (4-EPS), produced through dietary metabolism, is linked to chronic diseases but remains unexplored as a therapeutic agent for colorectal cancer (CRC) treatment. This study investigates the selective anticancer activity of 4-EPS using HCT-116 human colorectal adenocarcinoma cells and CCD 841 normal colon epithelial cells. Treatment with 4-EPS significantly reduced cell proliferation, viability, ATP levels, and colony-forming ability while increased apoptosis rate. Morphological changes included cell shrinkage, intracellular vesicle formation, and loss of membrane integrity. Mechanistically, 4-EPS upregulated Bax, downregulated Bcl2, and induced G2/M phase cell cycle arrest. In silico investigations revealed strong interactions with HDAC isoforms, suggesting epigenetic modulation. Markedly, 4-EPS treatment showed no deleterious effect on CCD 841 normal colon epithelial cells, which proved its selective anticancer role for colon cancer cells. These findings highlight 4-EPS as a promising therapeutic agent for treating CRC.
Insights
4-ethylphenyl sulfate (4-EPS), a gut microbe metabolite, shows selective anticancer effects against colorectal cancer (CRC) cells. This compound effectively reduced cancer cell growth and survival without harming normal colon cells, indicating therapeutic potential.
Area of Science:
- Oncology
- Microbiology
- Metabolomics
Background:
- Gut microbiota-derived metabolites are emerging as potential cancer therapeutics.
- 4-ethylphenyl sulfate (4-EPS), a dietary metabolite, has not been explored for colorectal cancer (CRC) treatment.
Purpose of the Study:
- To investigate the selective anticancer activity of 4-EPS against CRC cells.
- To explore the underlying mechanisms of 4-EPS action in HCT-116 cells.
Main Methods:
- In vitro assays using HCT-116 (CRC) and CCD 841 (normal colon) cells.
- Assessment of cell proliferation, viability, apoptosis, cell cycle, and morphology.
- In silico analysis of interactions with histone deacetylase (HDAC) isoforms.
Main Results:
- 4-EPS significantly inhibited proliferation, viability, and colony formation in HCT-116 cells.
- 4-EPS induced apoptosis and G2/M cell cycle arrest, with observed morphological changes.
- No significant toxicity was observed in normal CCD 841 cells, demonstrating selectivity.
- In silico analysis suggested potential epigenetic modulation via HDAC interactions.
Conclusions:
- 4-EPS exhibits selective anticancer activity against colorectal cancer cells.
- 4-EPS demonstrates potential as a novel therapeutic agent for CRC treatment.
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