Research Information System
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, vol.40, no.e70936, pp.1-12, 2026 (SCI-Expanded, Scopus)
Diphtheria toxin (DT) has been reported to exhibit cytotoxic effects in several cancer models; however, the molecular mechanisms underlying its apoptotic activity remain incompletely understood. In our previous study, DT was shown to induce cytotoxic and apoptotic responses in HT‐29 colorectal cancer cells, characterized by the upregulation of pro‐apoptotic genes and suppression of anti‐apoptotic signaling. Building on these findings, the present study aimed to explore the potential molecular context underlying DT‐induced transcriptional alterations using computational and bioinformatic approaches. Molecular protein–protein docking was performed to evaluate the possible interaction between DT and the anti‐apoptotic protein Bcl‐2. In parallel, previously obtained qRT‐PCR gene expression data from HT‐29 cells were reanalyzed to assess coordinated transcriptional responses associated with DT exposure. Network analysis using the STRING database indicated that DT‐responsive genes form a functionally connected interaction network associated with apoptosis, cellular stress responses, and cell‐cycle regulation. Principal component analysis and hierarchical clustering confirmed consistent differences in gene expression patterns between treated and control samples. Docking results suggested a potential interaction between DT and the BH3‐binding groove of Bcl‐2, supported by hydrogen bonding and hydrophobic contacts. Pathway enrichment analyses further linked the analyzed genes to apoptosis‐related pathways, including FoxO and p53 signaling. Collectively, these findings provide an integrated framework suggesting that DT‐induced cytotoxicity in HT‐29 cells may involve coordinated transcriptional responses and potential structural interaction with Bcl‐2, highlighting regulatory networks associated with apoptosis, cellular stress, and cell‐cycle control.