S-Adenosylmethionine Treatment of Colorectal Cancer Cell Lines Alters DNA Methylation, DNA Repair and Tumor...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Global DNA hypomethylation is a hallmark of colorectal carcinoma (CRC).
• S-adenosylmethionine (SAM), a methyl donor, shows tumor-inhibitory effects in some cancers, including CRC.
• The precise molecular effects of SAM on diverse CRC cell lines remain incompletely understood.

Purpose of the Study:

• To comprehensively evaluate the molecular impact of SAM treatment on colorectal carcinoma cell lines with distinct genetic profiles.
• To investigate SAM's effects on cell proliferation, gene expression, DNA methylation, and genomic stability.

Main Methods:

• Treatment of HT-29 and SW480 CRC cell lines with SAM (0.5 and 1 mmol/L for 48 h).
• Assessment of cell proliferation, senescence, cell cycle arrest (S phase).
• Whole-genome transcriptome and methylome analyses, DNA stability assays (γ-H2AX, micronucleus, comet assay), and exome sequencing.

Main Results:

• SAM reduced cell number and increased senescence via S phase arrest in both cell lines.
• Downregulation of epithelial-mesenchymal transition (EMT)-related genes (e.g., TGFB1) observed.
• Global DNA methylation levels were unchanged, but specific gene promoter methylation alterations occurred.
• SAM elevated γ-H2AX, suggesting DNA repair pathway activation (e.g., HUS1 upregulation).
• Enhanced genomic stability (decreased micronucleus, comet tail length) was noted exclusively in SW480 cells.

Conclusions:

• SAM demonstrates potential in reducing CRC progression by inducing senescence, DNA repair, and improving genome stability.
• Differential responses between HT-29 and SW480 cell lines underscore the necessity of molecular characterization for personalized methyl donor therapy in CRC.