ArticleBMC cancer2025
6-Aminonicotinamide enhances the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy for neuroblastoma.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPhotodynamic therapy (PDT) utilizing 5-aminolevulinic acid (5-ALA) as a photosensitizing precursor is an approved treatment modality for several types of cancers. However, the increased generation of antioxidants in cancer cells renders them resistant to PDT. MYCN-amplified neuroblastoma shows increased production of reactive oxygen species (ROS) and relies on the glutathione redox system for ROS detoxification. We tested the effectiveness of combining 6-aminonicotinamide (6-AN), a glucose-6-phosphate dehydrogenase inhibitor that modulates nicotinamide adenine dinucleotide phosphate and glutathione redox balance, with PDT for treating neuroblastoma.
methodsCellular protoporphyrin IX (PpIX) accumulation, cell proliferation, morphological changes, induction of cell death, redox status, and lipid peroxidation were evaluated in neuroblastoma cells treated with 5-ALA-mediated PDT with or without 6-AN.
results6-AN enhanced cytotoxicity of 5-ALA-mediated PDT in MYCN-amplified neuroblastoma cells. The enhanced efficacy was attributed to the increase in intracellular PpIX along with the suppression of the glutathione redox system. An analysis of cell death mechanisms revealed that 5-ALA-mediated PDT combined with 6-AN induced necrosis with lipid peroxidation.
conclusion6-AN enhances the cytotoxicity of 5-ALA-mediated PDT and promotes membrane lipid peroxidation in neuroblastoma cells. 5-ALA-mediated PDT combined with 6-AN could be a potential treatment strategy for neuroblastoma.
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