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NAD+ treatment decreases tumor cell survival by inducing oxidative stress
Cuiping Zhao1, Yunyi Hong, Jin Han
1Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, PR China.
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 micromolar 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.
Insights
Nicotinamide adenine dinucleotide (NAD+) treatment significantly reduces tumor cell survival by inducing oxidative stress. This selective effect on cancer cells suggests NAD+ as a potential novel cancer therapeutic agent.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Nicotinamide adenine dinucleotide (NAD+) is crucial for biological processes.
- NAD+ administration protects against brain damage and genotoxic agents.
- The impact of NAD+ on tumor cell survival remains unexplored.
Purpose of the Study:
- To investigate the effects of NAD+ on the survival of various tumor cell types.
- To elucidate the mechanisms underlying NAD+'s influence on tumor cell viability.
- To assess the potential of NAD+ as an anti-cancer therapeutic.
Main Methods:
- Treatment of C6 glioma and primary astrocyte cultures with NAD+ at varying concentrations (10 micromolar to 1 mM).
- Assessment of cell survival rates post-NAD+ exposure.
- Analysis of the roles of oxidative stress, P2X7 receptors, and calcium homeostasis.
Main Results:
- NAD+ treatment significantly decreased the survival of C6 glioma cells and other tumor cell types.
- NAD+ did not impair the survival of primary astrocyte cultures, indicating selectivity.
- Oxidative stress, P2X7 receptors, and altered calcium homeostasis were identified as key mediators.
Conclusions:
- NAD+ selectively reduces tumor cell survival, distinct from its effects on normal cells.
- The anti-tumor effects of NAD+ are mediated by induced oxidative stress.
- NAD+ presents a promising novel therapeutic strategy for cancer treatment.
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