Fluence-dependent infrared photobiomodulation remodels chromatin architecture to enhance chemosensitivity in head and neck tumors

Abstract

Photobiomodulation (PBM) therapy has emerged as a noninvasive therapeutic modality capable of modulating cellular processes through the targeted delivery of light. In this study, we investigated the effects of an infrared PBM on adenoid cystic carcinoma (ACC) cells, with a focus on fluence-dependent chromatin remodeling and the potential to enhance chemosensitivity to cisplatin. Using a range of energy densities, we observed that up to 26.6 J/cm² of PBM induces significant nuclear enlargement and modulates epigenetic markers by increasing histone H4K8 acetylation and decreasing trimethylation of histone H3K9. These changes recapitulate the effects of histone deacetylase inhibitors, previously shown to sensitize tumor cells to chemotherapy. Notably, pre-treatment with a 20 J/cm² fluence significantly enhanced cisplatin-induced cell death compared to sham controls, supporting the notion that an open chromatin state can potentiate chemotherapeutic efficacy. In contrast, higher fluences (≥ 33.3 J/cm²) led to a marked accumulation of DNA double-strand breaks and elevated reactive oxygen species, culminating in increased cell death. Additionally, while PBM consistently reduced cellular proliferation across fluences, it did not affect the migration potential of ACC cells. Owing to its high tissue penetrance, the infrared PBM presents a particularly novel and attractive approach for targeting deep-seated head and neck tumors, including those of salivary gland origin. Collectively, our findings suggest that lower-fluences of infrared PBM represents a safe and effective strategy to remodel tumor chromatin and enhance the chemosensitivity of head and neck cancers, paving the way for its integration into multimodal cancer treatment regimens.