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Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level.


ABSTRACT: Nicotinamide adenine dinucleotide (NAD) exists in an oxidized form (NAD+ ) and a reduced form (NADH). NAD+ plays crucial roles in cancer metabolism, including in cellular signaling, energy production and redox regulation. However, it remains unclear whether NAD(H) pool size (NAD+ and NADH) could be used as biomarker for colon cancer progression. Here, we showed that the NAD(H) pool size and NAD+ /NADH ratio both increased during colorectal cancer (CRC) progression due to activation of the NAD+ salvage pathway mediated by nicotinamide phosphoribosyltransferase (NAMPT). The NAMPT expression was upregulated in adenoma and adenocarcinoma tissues from CRC patients. The NADH fluorescence intensity measured by two-photon excitation fluorescence (TPEF) microscopy was consistently increased in CRC cell lines, azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC tissues and tumor tissues from CRC patients. The increases in the NAD(H) pool inhibited the accumulation of excessive reactive oxygen species (ROS) levels and FK866, a specific inhibitor of NAMPT, treatment decreased the CRC nodule size by increasing ROS levels in AOM/DSS mice. Collectively, our results suggest that NAMPT-mediated upregulation of the NAD(H) pool protects cancer cells against detrimental oxidative stress and that detecting NADH fluorescence by TPEF microscopy could be a potential method for monitoring CRC progression.

SUBMITTER: Hong SM 

PROVIDER: S-EPMC6361564 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level.

Hong Sun M SM   Hwang Sung W SW   Wang Taejun T   Park Chang W CW   Ryu Yeon-Mi YM   Jung Jin-Hak JH   Shin Ji H JH   Kim Sang-Yeob SY   Lee Jong L JL   Kim Chan W CW   Yoon Gyesoon G   Kim Ki H KH   Myung Seung-Jae SJ   Choi Kwan Y KY  

Cancer science 20181227 2


Nicotinamide adenine dinucleotide (NAD) exists in an oxidized form (NAD<sup>+</sup> ) and a reduced form (NADH). NAD<sup>+</sup> plays crucial roles in cancer metabolism, including in cellular signaling, energy production and redox regulation. However, it remains unclear whether NAD(H) pool size (NAD<sup>+</sup> and NADH) could be used as biomarker for colon cancer progression. Here, we showed that the NAD(H) pool size and NAD<sup>+</sup> /NADH ratio both increased during colorectal cancer (CRC)  ...[more]

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