Suberoylanilide hydroxamic acid suppresses gastric cancer cell growth through apoptosis induction, mitochondrial dysfunction, and modulation of nucleotide metabolism-associated genes
Year: 2025
Type: article
Abstract: Gastric cancer (GC) remains a major global health challenge due to its aggressive nature and resistance to conventional therapies. (SAHA, vorinostat), a histone deacetylase (HDAC) inhibitor, exhibits potent anticancer effects in various malignancies. However, its specific mechanisms in GC require further elucidation. The current study aimed to clarify the anticancer potential of SAHA against GC, focusing on apoptosis induction, mitochondrial dysfunction, cell cycle alteration, and gene expression related to nucleotide metabolism and cell cycle progression. SAHA significantly reduced GC cell proliferation, with adenocarcinoma (AGS) cells showing a pronounced response. Further experiments with AGS cells demonstrated that SAHA treatment substantially increased late apoptotic cell populations and mitochondrial depolarization, indicating activation of mitochondrial-mediated apoptosis. Cell cycle analysis revealed an increased apoptotic subG1 fraction, linking apoptosis to disrupted cell cycle progression. Quantitative PCR analyses indicated that SAHA treatment markedly altered expression levels of key genes associated with nucleotide synthesis and cell cycle regulation. Specifically, thymidylate synthase (TYMS) expression was significantly downregulated, suggesting compromised DNA synthesis capacity. Conversely, thymidine phosphorylase (TYMP), involved in nucleotide salvage pathways, was notably upregulated. In conclusion, SAHA exerts significant anticancer activity in GC cells via apoptosis induction, mitochondrial dysfunction, cell cycle arrest, and modulation of nucleotide metabolism-related genes. These findings indicate the therapeutic potential of SAHA in GC management.
Source: Journal of Hazard Literacy
DOI: 10.63737/jhl.25.0018
Authors: Nayeon Kim, Seoungdong Kim
Institution: Chosun University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4410529235