Reduced
nicotinamide adenine dinucleotide (
NADH) plays key roles in energy metabolism and mitochondrial functions. However, there has been little information regarding the effect of
NADH on cell survival. In this study we determined the effect of
NADH treatment on the survival of
glioma cells. We found that treatment of C6
glioma cells with as low as 1 μM
NADH for 24 hrs significantly decreased the survival of these cells, and that treatment of the cells with 1000 μM
NADH for 4 days decreased the survival of the cells by nearly 90%. This effect of
NADH on
glioma cells appears to be mediated by oxidative stress, as indicated by our findings that
NADH treatment induced an increase in intracellular
reactive oxygen species, and that two
antioxidants, N-acetyl
cysteine and
Trolox, significantly attenuated the effect of
NADH. We also found that
NADH treatment induced an increase in
poly(ADP-ribose) polymerase (PARP) activity, and that
PARP inhibitors decreased the effect of
NADH on the survival of
glioma cells. These observations suggest that
NADH reduces the cell survival at least partially by activating PARP. Collectively, our studies demonstrated a novel
biological property of
NADH -
NADH decreases
glioma cell survival by increasing oxidative stress and PARP activation. These results also suggest that
NADH may have therapeutic potential for treating
gliomas.