NAD+ induces C6 glioma cell death by generating oxidative stress and increasing intracellular calcium concentrations

NAD+ plays important roles in various biological processes. We have found that while it is highly protective against oxidative stress‐induced death of primary neuronal cultures and astrocyte cultures, NAD+ can induce glioma and neuroblastoma cell death. In this study we investigated the mechanisms underlying the effects of NAD+ on C6 glioma cells. We found that two antioxidants, Trolox and N‐acetyl cysteine, can markedly decreased the NAD+‐induced glioma cell death, suggesting that oxidative stress mediates the effects of NAD+ on the cell death. Our study has also shown that BAPTA‐AM, a calcium chelator, also largely prevented NAD+‐induced decreases in the cell survival, suggesting a critical role of elevated intracellular calcium concentrations in the cell death. Collectively, our study has provided novel evidence that NAD+ treatment can induce oxidative stress and impaired calcium homeostasis in such tumor cell types as C6 glioma cells, which leads to decreased survival of the tumor cells. (Supported by a Key Basic Research Grant from Shanghai Educational Committee (to WY) and by a Pujiang Scholar Award (to WY)).