Niacin Protects iPSC-Derived Neurons from Chemotherapy-Induced Toxicity.

Neurotoxicity remains a major dose-limiting adverse effect of cancer therapy. Previous studies have indicated that niacin can promote neuroprotective effects primarily through antioxidative mechanisms. In this study, we investigated the neuroprotective role of niacin on human induced pluripotent stem cell-derived motor neurons (iPSC-MNs) subjected to three neurotoxic chemotherapeutic agents: cisplatin, methotrexate, and 5-fluorouracil. Our findings revealed that niacin significantly enhanced neuronal viability, as evidenced by MTT and LDH assays, with the most pronounced protection observed in 5-fluorouracil–treated iPSC-MNs. Moreover, niacin markedly reduced reactive oxygen species (ROS) generation across all chemotherapy treatment conditions. Additionally, niacin mitigated mitochondrial membrane potential (MMP) decrease and promoted ATP production, indicating its ability to counteract chemotherapy-induced mitochondrial dysfunction. Collectively, our results highlight the potential of niacin as a form of supportive therapy for the protection of neurons against CIN and demonstrate the utility of iPSC-derived neurons as a relevant model for investigating various forms of CIN including chemotherapy-induced peripheral neuropathy (CIPN) or cognitive impairment (CICI).