[Frontiers in Bioscience E3, 434-441, January 1, 2011]

NAD+ treatment decreases tumor cell survival by inducing oxidative stress

Cuiping Zhao1, Yunyi Hong1, Jin Han1, Yingxin Ma1, Heyu Chen1, Weiliang Xia1, Weihai Ying1,2

1Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P.R. China, 2Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Materials
3.2. Cell cultures
3.3. Experimental procedures
3.4. Lactate dehydrogenase (LDH) assay
3.5. Trypan blue assay
3.6. Flow cytometry-based prodium iodide (PI) staining
3.7. Dihydroethidium (DHE) assay
3.8. Statistical analyses
4. Results
4.1. NAD+ treatment decreased the survival of various types of tumor cells
4.2. Oxidative stress mediates the effects of NAD+ on C6 glioma cells
4.3. P2X7 receptors and altered calcium homeostasis are involved in the effects of NAD+ on tumor cell survival
4.4. Nicotinamide treatment did not affect the survival of C6 glioma cells
5. Discussion
6. Acknowledgment
7. References

1. ABSTRACT

NAD+ plays important roles in various biological processes. It has been shown that NAD+ treatment can decrease genotoxic agent-induced death of primary neuronal and astrocyte cultures, and NAD+ administration can reduce ischemic brain damage. However, the effects of NAD+ treatment on tumor cell survival are unknown. In this study we found that treatment of NAD+ at concentrations from 10 M to 1 mM can significantly decrease the survival of various types of tumor cells such as C6 glioma cells. In contrast, NAD+ treatment did not impair the survival of primary astrocyte cultures. Our study has also indicated that oxidative stress mediates the effects of NAD+ on the survival of tumor cells, and P2X7 receptors and altered calcium homeostasis are involved in the effects of NAD+ on the cell survival. Collectively, our study has provided the first evidence that NAD+ treatment can decrease the survival of tumor cells by such mechanisms as inducing oxidative stress. Because NAD+ treatment can selectively decrease the survival of tumor cells, NAD+ may become a novel agent for treating cancer.