Novel Synthetic Compound IIIJ Induces Bidirectional Modulation of miR-155 and Apoptosis in Oral Squamous Cell Carcinoma

Abstract

ackground: Head and neck squamous cell carcinoma (HNSCC), particularly oral squamous cell carcinoma (OSCC), remains therapeutically challenging due to recurrence and resistance. Although agents such as doxorubicin are effective, their clinical use is limited by non-selective toxicity. This study investigated the antitumor efficacy, mechanistic actions, and molecular interactions of a novel synthetic compound, IIIJ (T1), compared with doxorubicin in OSCC. Methods: Cytotoxic activity was assessed in HNO-97 OSCC cells and normal human skin fibroblasts (HSF) using standard viability assays. Cell cycle progression and apoptosis were analyzed by flow cytometry following propidium iodide staining. miR-155 expression was quantified by qRT-PCR. A protein–protein interaction (PPI) network analysis was conducted to identify potential biological targets and pathways related to DNA repair, epithelial–mesenchymal transition (EMT), and immune regulation. Results: IIIJ exhibited selective anticancer activity with a Selectivity Index of 1.08 and reduced OSCC cell viability by 13%. Unlike doxorubicin, which induced marked G0/G1 arrest and apoptosis in normal fibroblasts, IIIJ preserved normal cell cycle integrity with minimal off-target toxicity. IIIJ produced differential modulation of miR-155, suppressing its expression by 97% in fibroblasts while inducing a 45-fold increase in OSCC cells, whereas doxorubicin caused non-selective upregulation. PPI network analysis highlighted key associations with CLDN/CDH1, PARP1/BRCA, and PD-L1 signaling clusters. Conclusion: IIIJ demonstrates a favorable therapeutic profile characterized by selective cytotoxicity, minimal normal-cell toxicity, and dynamic miR-155 modulation. These features, combined with its engagement of DNA repair and immune-related pathways, support its potential as a promising candidate for combination strategies in OSCC therapy.