Synergistic Effects of 5-Azacitidine and Photodynamic Therapy Using Spirulina Platensis on Cell Death in Cal27 Oral Squamous Cell Carcinoma Cells Publisher Pubmed



Ranjbar A ; Shahabi S ; Alaeddini M ; Mohammadpour H ; Hodjat M ; Saberi S
Source: Photodiagnosis and Photodynamic Therapy Published:2025

Abstract

Background: Oral squamous cell carcinoma (OSCC) remains a major clinical challenge with high mortality and limited treatment responsiveness. Epigenetic therapy with 5-azacitidine (5-aza), a DNA methyltransferase inhibitor, and photodynamic therapy (PDT) using natural photosensitizers have independently shown promise in enhancing cancer cell death. Objective: This study investigates the synergistic effect of combining 5-aza and Spirulina-based PDT on OSCC cells. Methods: Human OSCC (CAL27) and normal gingival fibroblast (HGF) cells were treated with 5-aza, Spirulina extract-based PDT, or their combination. Cytotoxicity was evaluated by MTT assay; migration by wound healing; invasion by MMP2/9 gene expression; apoptosis by flow cytometry; and DNA fragmentation by comet assay. Results: The combination therapy significantly reduced CAL27 cell viability while sparing normal HGF cells. Cell migration and invasion were markedly suppressed, with downregulation of MMP2 and MMP9. Apoptosis rates and DNA damage were significantly higher in the combined treatment group than in either monotherapy. Conclusion: Spirulina-based PDT enhances the antitumor efficacy of 5-aza in OSCC by inducing synergistic cytotoxic, apoptotic, and anti-invasive effects. These findings support the therapeutic potential of combining epigenetic and oxidative stress-based modalities in OSCC management. © 2025 Elsevier B.V., All rights reserved.